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baTumis SoTa rusTavelis saxelmwifo universiteti
ganaTlebis da mecnierebaTa fakulteti
biologiis departamenti
sofiko cqvitiniZe
„tuberkulozis sensitiur da rezistentul formebTan
sisxlis jgufuri antigenebis (ABO; Rh-Hr; MN; Kell)
asocirebis da daavadebulTa humoruli imunuri statusis
Seswavla saqarTveloSi mcxovreb eTnikur populaciebSi“
biologiis doqtoris akademiuri xarisxis mosapoveblad
warmodgenili disertacia
specialobiT - adamianis populaciebis genetika
xelmZRvanelebi: prof. r. xuxunaiSvili
prof. k. vaWaraZe
baTumi
2013
2
S i n a a r s i
Sesavali ----------------------------------------------------------------------------------------------------- 4
terminTa ganmarteba------------------------------------------------------------------------------------ 10
Tavi I. literaturuli mimoxilva ------------------------------------------------------------- 12
I.1. tuberkulozis epidemiologia, misi kontrolisa da prevenciis
Tanamedrove strategiebi ---------------------------------------------------------------------------- 12
I.2. tuberkulozis epidemiologia saqarTveloSi ------------------------------ 17
I.3. tuberkulozis gamomwvevi - Mycobacterium tuberculosis ------------------------- 21
I.3.1. mikobaqteriis rezistentobis ganmapirobebeli faqtorebi------------ 24
I.4. rezistentuli tuberkulozis globaluri epidemiologia da
etiologia ---------------------------------------------------------------------------------------------------------- 26
1.5. multifaqtoruli daavadebebi da populaciebis genetikuri
polimorfizmi ---------------------------------------------------------------------------- 28
I.5.1 eriTrocituri jgufuri antigenebi da maTi asociaciuri kavSirebi
sxvadasxva tipis paTologiebTan ---------------------------------------------------------- 32
I.6. organizmis imunuri dacvis meqanizmebi mikobaqteriis mimarT
ganviTarebul imunur pasuxSi -------------------------------------------------------------- 44
I.7. tuberkulozi da M. tuberculosis mimarT organizmis mgrZnobelobaSi
monawile genebi ------------------------------------------------------------------------------- 53
Tavi II. kvlevis masala da meTodebi--------------------------------------------- 62
II.1. kvlevis masala ------------------------------------------------------------------ 62
II.2. kvlevis meTodebi --------------------------------------------------------------- 63
II.2.1. imunoserologiuri meTodebi --------------------------------------------- 63
II.2.2. biostatistikuri analizis meTodebi ----------------------------------- 64
II.2.3. kvlevis molekulur-bioqimiuri meTodebi-------------------------------- 66
II.2.4. imunologiuri analizis meTodebi ----------------------------------------- 43
Tavi III. Kkvlevis Sedegebi ------------------------------------------------------------------------ 77
3
III.1. filtvis tuberkulozis sensitiuri da wamalrezistentuli
formebs asocireba АВ0, Rh-Hr, Kell, MN sistemis eriTrocitur jgufur
antigenebTan qarTul populaciaSi ------------------------------------------------------------ 77
III.1.1. sensitiuri da wamalrezistentuli tuberkulozis asocireba
eriTrocituri jgufuri sistemebis (ABO, Rh, MN) alelebTan saqarTveloSi
mcxovreb azerbaijanul populaciaSi-------------------------------------------------------------- 98
III.1.2. eriTrocituri ABO (r,p,q), Rh-Hr (RhD+,RhD-) da MN (p,q) jgufuri
sistemis alelTa gavrcelebis SedarebiTi analizi tuberkuloziT
daavadebul qarTul da azerbaijanul populaciebSi --------------------------- 105
III. 2. IgM, IgG da IgA done filtvis tuberkuloziT daavadebul
populaciaSi ----------------------------------------------------------------------------------------------------- 109
III.3. SLC11A1 genis D543N lokusis polimorfizmis Seswavla filtvis
tuberkulozis wamalrezistentuli da sensitiuri formebiT daavadebul
pacientebSi -------------------------------------------------------------------------------------------------------- 121
daskvnebi ---------------------------------------------------------------------------------------------------- 129
gamoyenebuli literatura ----------------------------------------------------------------------- 131
4
Sesavali
tuberkulozi Mycobacterium tuberculosis-is paTogenuri agentiT gamowveuli
infeqciuri daavadebaa, romelic uZvelesi droidan moyolebuli dRemde
sazogadoebis janmrTelobis seriozul problemas warmoadgens. M.
tuberculosis infeqciuri agenti msoflioSi yovelwliurad 2-3 mln adamianis
sikvdilis mizezi xdeba, xolo msoflio mosaxleobis 1/3 inficirebulia
aRniSnuli paTogeniT da daavadebis klinikuri ganviTarebis mudmivi
safrTxis winaSe dgas. tuberkulozi gansakuTrebiT mwvave problemas
warmoadgens ganviTarebad qveynebSi. daavadebis SemTxvevebis 95%
aRmosavleT aziis, afrikis, laTinuri amerikis da aRmosavleT evropis
qveynebze modis, maT Soris sakmaod mniSvnelovani sixSiriT _ postsabWoTa
sivrceze, sadac mosaxleobis 55% infeqciuri agentis matarebelia. bolo
wlebSi daavadebis SemTxvevaTa matebis tendencia gamovlinda iseT
ganviTarebul qveynebSi, rogoricaa aSS, dasavleT evropisa da skandinaviis
qveynebi.
tuberkulozis problema mwvaved dgas saqarTveloSic. janmrTelobis
msoflio organizaciis monacemebiT, saqarTvelo 27-e adgilzea im
qveynebs Soris, sadac daavadebis maRali prevalentoba fiqsirdeba. Tumca,
ukanaskneli 10 wlis monacemebiT, tuberkulozis aRniSnuli maCvenebeli
met-naklebad stabiluria antituberkulozuri programebis moqmedebis
Sedegad. magram, sagangaSo mdgomareobas qmnis wamlis mimarT rezistentuli
tuberkulozis SemTxvevebis zrda. situacias kidev ufro amZimebs pirveladi
rezistentobis axal SemTxvevaTa maRali maCvenebeli.
tuberkulozi multifaqtorul daavadebaTa (mfd) ricxvs miekuTvneba. M.
Tuberculosis CxiriT inficirebis SemTxvevaSi daavadebis klinikur
ganviTarebaze mravali faqtori moqmedebs, romelTagan aRsaniSnavia:
ekonomikuri mdgomareoba (cxovrebis done), individis mgrZnobeloba
infeqciisadmi, asaki, kvebis racioni, koinfeqciebis arseboba, emociuri da
fizikuri stresi, samedicino momsaxurebis done da xelmisawvdomoba,
5
higienuri pirobebi, SesaZloa, individis sqesic da aS. Tumca, xSiria
SemTxvevebi, roca adamianebi inficirdebian, magram ar avaddebian zemoT
CamoTvlili faqtorebis arsebobis SemTxvevaSic ki. am mosazrebas isic
adasturebs, rom daavadeba klinikuri saxiT tuberkulozis CxiriT
inficirebulTa 10%-Si viTardeba, xolo 90% infeqciis matareblad rCeba
mTeli sicocxlis manZilze. bolo periodis mecnieruli kvlevebis Tanaxmad
(Ryu et al., 2000; Remus et al., 2004; Deglado et al., 2002; Li et at al., 2006; Takahashia et al.,
2008; Tamaria et al., 2010; Tyagi et al., 2010), tuberkulozis klinikur ganviTarebaSi
garemo faqtorebTan erTad arsebiT rols asrulebs individis genetikuri
konstitucia, romelic gansazRvravs daavadebisadmi sensibilobas an misdami
organizmis mdgradobas.
yovel cocxal organizms gaaCnia Tavisi individualuri genotipi,
romelic konkretulad misTvis damaxasiaTebel genTa nakrebs Seicavs.
genomSi arsebuli calkeuli geni an genTa jgufi pasuxismgebelia
organizmis gansazRvrul niSan-Tvisebaze. maT Soris aris genebi, romlebic
daavadebaTa mimarT organizmis sensibilobas an mdgradobas gansazRvravs.
aRniSnul genebSi momxdari, Tundac, erTnukleotidiani cvlileba
genetikur polimorfizms ganapirobebs da paTogenuri agentebis mimarT
organizmis gansxvavebuli mgrZnobelobis safuZvels warmoadgens. amasTan,
multifaqtoruli daavadebebis didi nawili eTnospecifikuri
winaswarganpirobebulobiT xasiaTdeba. Cveulebriv, adamianTa eTnikuri
jgufebi genTa SemadgenlobiT Wrelia, rac daavadebebis gamovlenis
sixSiriT da maTi ganmapirobebeli faqtorebis variabelobiT gamoixateba.
fiqsirdeba daavadebaTa sensibilizaciis gansxvavebuli maCveneblebi,
Tundac, erTi da igive teritoriaze mcxovreb eTnikur populaciebSi.
swored amitom, populaciur doneze, xSirad, daavadebaTa mimarT
gansxvavebuli midrekileba ikveTeba. aris populaciebi, romlebic advilad
eqvemdebarebian romelime konkretul daavadebas, maSin, roca sxvebi am
daavadebis mimarT bunebrivi mdgradobiT gamorCevian.
6
adamianTa eTnoteritoriuli jgufebis formireba Sesabamis saarsebo
garemo piobebTan urTierTobaSi xangrZlivi evoluciuri procesis Sedegia
da maTi genofondis Tanamedrove struqtura istoriuli ganviTarebis
sxvadasxva etapze Camoyalibda. am procesebis safuZvelze eTnikur
populaciebSi, erTi mxriv, adgili aqvs mfd-is genuri lokusebis
cvalebadobis farTo diapazonis Camoyalibebas, meore mxriv ki, im
haplotipebis struqturul unikalobas, sadac esa Tu is konkretuli genia
lokalizebuli. aqedan gamomdinare, gansxvavebul eTnosebSi mfd-is genebi
imyofeba gansxvavebul alelur mdgomareobasa da garemocvaSi, rac
gavlenas axdens konkretuli genis fenotipur gamovlenaze da xSir
SemTxvevaSi gansazRvravs daavadebis mimarT winaswarganpirobebulobas.
kvlevebiT gamovlenili iqna, rom eTnosebis garkveuli nawili metad
sensibiluria tuberkuloziT daavadebis mimarT, maSin, roca sxvebs
Camoyalibebuli aqvT e.w. „populaciuri imuniteti“, rasac im alelebis
evoluciuri gacxrilvis procesiT xsnian, romlebTanac mkacradaa
asocirebuli Sesabamisi daavadebebi.
daavadebebis winaswarganpirobebulobaSi CarTuli genebis kvleva
warmoebs, rogorc uSualod genis struqturis SeswavliT, aseve mis mier
myarad determinirebuli fenotipuri niSnebiT. eriTrocituri jgufuri
antigenebi aseT fenotipur niSans warmoadgens. aRniSnuli antigenebiT
determinirebuli gansxvavebuli fenotipuri jgufebi da, Sesabamisad, maTi
imunogenetikuri lokusebi gansxvavebulad arian midrekilni ama Tu im
daavadebis ganviTarebisken, rogorc individis, ise eTnikuri jgufebis
doneze. eriTrocituri jgufuri sistemebis antigenebisa Tu haplotipebis
kvlevisas xSirad vlindeba maTi korelacia sxvadasxva infeqciur Tu
arainfeqciur daavadebasTan.
infeqciuri daavadebis mimdinareobisas aqtiuradaa CarTuli organizmis
imunuri sistema. tuberkulozis sxvadasxva klinikuri formis dros,
namkurnalev Tu pirvelad pacientebSi, samkurnalwamlo preparatebis
mimarT sensitiur da rezistentul formebSi organizmis imunuri sistema
gansxvavebulad reagirebs ujreduli an humoruli imunuri meqanizmebiT.
7
Sesabamisad, organizmis imunuri statusi gansxvavebulia. informacia
organizmis imunuri statusis Sesaxeb genetikur faqtorebTan erTad srul
suraTs iZleva daavadebis riskis Sefasebisa da drouli prevenciuli
RonisZiebebis gatarebisTvis.
infeqciuri daavadebis ganviTarebaze pasuxismgebeli genebis umetesi
nawili CarTulia organizmis imunuri dacvis meqanizmebSi. dReisaTvis
Seswavlilia tuberkulozisadmi winaswarganpirobebulobis mravali geni
(SLC11A1, TLR, HLA, TNF-α, VDR, IL10, TGFβ, TGFβ da a.S.) da maTi polimorfuli
variaciebis asociaciuri kavSirebi tuberkulozis mimarT mosalodnelobasa
da daavadebisadmi mdgradobasTan. dawyebulia rezistentuli tuberkulozis
genetikuri aspeqtebis kvleva. arsebul monacemebze dayrdnobiT, ikveTeba
adamianis organizmis genetikuri struqturis mniSvneloba wamlis mimarT
rezistentuli tuberkulozisadmi organizmis midrekilebasa Tu
mdgradobasTan mimarTebaSi.
Temis aqtualoba. tuberkulozis gavrcelebis maRali maCvenebeli
saqarTveloSi daavadebis kontrolis da prevenciis efeqturi RonisZiebebis
gatarebis aucileblobas ganapirobebs. es SesaZlebelia, miRweul iqnes,
erTi mxriv, daavadebis klinikuri marTvis meTodebis srulyofiT, meore
mxriv, profilaqtikuri RonisZiebebis SemuSavebiT. daavadebisadmi
midrekili „maRali riskis“ jgufebis gamoyofa SemdgomSi maT mimarT
prevenciuli zomebis SemuSavebis safuZvels warmoadgens.
Tanamedrove genetikisa da genomikis ganviTarebasTan erTad gaizarda
paTogenuri procesebis marTvis SesaZlebloba. eriTrocituri jgufuri
antigenebis, rogorc genetikurad myari niSnis Seswavla, tuberkuloziT
daavadebulebSi jansaR donorebTan mimarTebaSi, SesaZlebels xdis,
gamoiyos daavadebisadmi midrekili risk-jgufebi da maT mimarT
ganxorcieldes profilaqtikuri RonisZiebebi. tuberkulozTan
asocirebuli genebis (maT Soris eTnospecifikuri) da maTi polimorfuli
variaciebis gamovlena, agreTve, recipientis imunuri reaqciis Seswavla
8
tuberkulozis diagnostikis axali meTodebis Ziebis da vaqcinaciis axali
midgomebis SemuSavebis saSualebas iZleva.
aRniSnul monacemebze dayrdnobiT, SesaZlebelia eTnikuri jgufis Tu
organizmis daaavadebis mimarT sensibilobis an mdgradobis winaswari
prognozireba, rac, saboloo jamSi, daavadebis ukeT kontrolis
ganxorcielebis saSualebas iZleva.
saqarTveloSi mcxovrebi eTnikuri populaciebi am mimarTebiT dRemde
ar iyo Seswavlili.
kvlevis mizani. zemoT aRniSnulidan gamomdinare, kvlevis mizans
warmoadgenda:
filtvis tuberkuloziT daavadebul pacientebSi genetikurad
determinirebuli faqtorebis _ eriTrocituri jgufuri antigenebis
gavrcelebis Taviseburebebis Seswavla da maTTan daavadebis SesaZlo
asociaciuri kavSirebis gamovlena;
eriTrocituri jufuri antigenebis mixedviT tuberkulozisadmi
mgrZnobiare fenotipebisa da alelebis gamoyofa da daavadebisadmi
midrekili maRali risk-jgufebis gamovlena saqarTveloSi mcxovreb
eTnikur (qarTuli, azerbaijanuli) populaciebSi;
organizmSi tuberkulozis infeqciuri agentisadmi ganviTarebuli
humoruli imunuri pasuxis Seswavla antituberkulinuri specifikuri Tu
saerTo antisxeulebis donis gamovlenis safuZvelze daavadebis sxvadasxva
klinikuri formis dros;
SLC11A1 genis D543N lokusis polimorfizmis Seswavla filtvis
tuberkulozis sensitiuri da rezistentuli formiT daavadebul qarTul
populaciaSi.
kvlevis amocanebi:
eriTrocituri jgufuri sistemebis (ABO, Rh, Kell, MN) antigenebis,
fenotipebis, maTi ganmsazRvreli alelebis da haplotipebis gavrcelebis
9
Taviseburebebis Seswavla filtvis tuberkulozis sensitiur da wamlis
mimarT rezistentul formebSi;
eriTrocituri jgufuri sistemebis korelaciuri kavSiris
gamovlena filtvis tuberkulozTan da daavadebis mimarT maRali risk-
jgufebis gamoyofa daavadebul qarTul da azerbaijanul populaciaSi;
antituberkulinuri imunoglobulinebis jamuri da
imunoglobulinebis (IgA+G+M) saerTo donis SeswavliT daavadebulTa
humoruli imunuri statusis Sefaseba pirvelad da namkurnalev pacientebSi,
filtvis tuberkulozis sensitiuri, rezistentuli da gansxvavebuli
simZimis klinikuri (infiltraciuli, kerovani, fibro-kavernozuli)
formebis dros;
infeqciuri daavadebis mimarT organizmis bunebriv rezisten-
tobasTan asocirebuli makrofaguli NRAMP1 cilis makodirebeli SLC11A1
genis D543N lokusis polimorfizmis Seswavla filtvis tuberkulozis
sensitiur da rezistentul formebSi.
10
terminTa ganmarteba
mfd – multifaqtoruli daavadebebi
ftb – filtvis tuberkulozi
BCG- (Bacilli Camlet_Guerine) kamlet-guerinis vaqcina
CFU – (Colony Forming Unit) – kolonia-warmomqmneli erTeuli
DOTS – (Directly observed treatment, short course) meTvalyureobis qveS
E - eTanbutoli
GWAS - Genome-wide Association Study- genomis masStabis asosiaciuri kvleva
HLA- (Human Leukocyte Antigen) adamianis leikocituri antigeni
IL- (Interleukin) interleikini
IFN γ – (Interferon γ) interferoni-gama
INH/H - izoniazidi
Ig- (Immunoglobulin) - imunoglobulini
LAM – (LipoArabinoManan) - lipoarabinomanani
MDR TB -(multidrug-resistant Tuberculosis) –multirezistentuli tuberkulozi
MHC- (Major Histocompatibility Complex)- histoSeTavsebulobis mTavari
kompleqsi
PAMP – (Pathogen Assocciated Molecular patterns) -paTogenTan asocirebul
molkulebi
PAS – (Para-Aminosalicylate Sodium) –para-aminosalicilatis marili
PZA - pirazinamidi
R – rifampicini
S - streptomicini
SLC11A1- SoLute Carrier family 11 member 1 gene – bunebriv rezistentobasTan
asocirebuli makrofaguli cila-1-is makodirebeli geni
SNP- single nucleotide polimorfism – erTnukleotidiani polimorfizmi
TGFβ -(Transforming Growth Factor β) -matransformirebeli zrdis faqtori β
11
TLR- (Toll Like Receptor) – tolis msgavsi receptori
TNF-α - Tumor Necrosis Factor α – simsivnis nekrozis faqtori-α
VDR – Vitamin D Receptor – vitamin D-s receptori
USAID - United States Agency for International Development – aSS-s serTaSoriso
ganviTarebis saagento
12
Tavi I
literaturuli mimoxilva
I .1. tuberkulozis epidemiologia, misi kontrolisa da prevenciis
Tanamedrove strategiebi
tuberkulozi antikuri xanidan momdinare daavadebaa, romelic am
droidanve iyo sazogadoebis janmrTelobis seriozuli problema.
Mycobacterium tuberculosis-is gvari 150 000 wlis win warmoiSva (Daniel., 2006). Zv.w.aR.-
iT daTariRebuli egviptisa da andebis mumiebSi, egvipturi da kolumbiuri
xelovnebis nimuSebSi napovnia ConCxis tipuri tuberkulozuri
deformaciebi (Nerlich et al., 1997; Donoghue et al., 2004; Palomino et al., 2007).
Mycobacterium bovis-iT gamowveuli tuberkulozuri anomaliebi Cv.w.aR-mde 8000
wliT daTariRebul Crdilo evropisa da aziis namarxebSic aris napovni (Cosivi
et al., 1995; Behera., 2010).
„fTizis“ (filtvebis anTeba) pirvelad daaxloebiT Zv.w.aR-iT 60 wels
berZnul literaturaSi hipokrates mier iqna moxseniebuli, rogorc im
droisTvis yvelaze gavrcelebuli momakvdinebeli daavadeba. me-17
saukunidan tuberkulozi evropaSi „TeTri Wiri“-s saxeliT TiTqmis ori
saukune mZvinvarebda. am periodidan daiwyo daavadebis paTanatomiuri
Seswavla. tuberkuloziT gamowveuli sikvdilianobis maCvenebelma Zalian
maRal niSnuls 1650 wels miaRwia. populaciebis maRali simWidrove, cudi
sanitaruli mdgomareoba, romelic im drois evropisa da Crdilo
amerikisTvis tipur suraTs warmoadgenda, paTogenis gavrcelebisTvis
srulyofil garemos qmnida (Palomino et. Al., 2007).
simptomebis mravalferovnebis gamo tuberkulozuri daavadebis
identifikacia me-19 saukunis pirvel naxevarSi Zalian rTuli iyo. Semdgomma
mecnierulma aRmoCenebma daavadebis ara Tu identifikacia, aramed misi
prevalentobis maCveneblis Semcireba, garkveulwilad kontroli da
13
prevenciuli RonisZiebebis gatarebac ki gaxada SesaZlebeli. 1882 wels
robert koxis mier identificirebuli iqna infeqciuri agenti, xolo 1921 wels
kamletisa da guerinis mier gamoyofili iqna tuberkulozis baqteriis
specifikuri, dabalvirulenturi Stami, romelic safuZvlad daedo BCG
vaqcinis Seqmnas da miuxedavad misi arasakmarisi efeqturobisa, igi dResac
erTaderTi tubsawinaaRmdego vaqcinaa. ukanasknel wlebSi aqtiurad
mimdinareobs muSaoba axali vaqcinis dizainze (Montanes et al., 2011).
1895 wels rentgenis sxivebis aRmoCenam SesaZlebeli gaxada swori
diagnostireba. 1944 wlidan daiwyo tubsawinaaRmdego qimioTerapiis era,
romelic ukavSirdeba vaqsmanis da satzis mier antibiotik streptomicinis
mignebas streptomicinis Semdeg medicina mivida izoniazidamde.
tubsawinaaRmdego preparatebiT mkurnalobam garkveulwilad Seamcira
tuberkuloziT avadobisa da sikvdilianobis maCvenebeli. im periodisTvis
mTel rig qveynebSi realurad arsebobda tuberkulozis kontrolis
SesaZlebloba, magram me-20 saukunis 80-iani wlebidan msoflioSi kvlav
aRiniSna tuberkulozis SemTxvevaTa mateba da daavadebis globaluri
Semoteva. tubsawinaaRmdego wamlebis mimarT mikobaqteriis rezistentuli
Stamebis warmoSobam da gavrcelebam arsebuli problema kidev ufro
gaaRrmava (Palomino et al., 2007).
sadReisod, tuberkulozi, ara marto samedicino, aramed sxva dargebis
(genetikuri, imunogenetikuri, imunologiuri) kvlevebis fokusSi moeqca.
Tanamedrove mecnieruli kvlevebiT xdeba daavadebis winaswar-
ganpirobebulobis Seswavla molekuluri donidan eTnikur-populaciur
donemde. mecnierebi cdiloben, miagnon daavadebis prevenciis da kontrolis
ukeTes meqanizmebs, axali qimioTerapiuli medikamentebisa da srulyofili
vaqcinis Seqmnis gzebs (Schulger & Rom, 1998; Casanova & Abel, 2002). aRniSnuli
Zalzed mniSvnelovania janmrTelobis usafrTxoebis organizebis,
profilaqtikis, diagnostirebis, mkurnalobis da daavadebasTan brZolis
programebis SesamuSaveblad.
14
yovelwliurad tuberkulozis CxiriT msoflios mosaxleobis 1/3
inficirdeba, xolo 2 mln. adamiani daavadebis mZime formiT iRupeba.
janmrTelobis msoflio organizaciis masalebiT, tuberkulozi gavrcelebis
mixedviT meSvide adgilzea, mis mier gamowveuli sikvdilianobis maCvenebliT
ki _ mexuTeze (WHO, 2012). daavadebaTa kontrolis programebis,
antituberkulozuri medikamentebis, prevenciuli RonisZiebebis miuxedavad,
tuberkulozis epidemiologiuri prognozi sakmaod SemaSfoTebelia.
magaliTad, afrikis zogierT qveyanaSi tuberkuloziT daavadebulTa
ricxvma 50%-s gadaaWarba. mecnierebis prognoziT, Tu daavadebis
sawinaaRmdegod intensiuri RonisZiebebi ar iqna gatarebuli, arsebuli
mdgomareoba 2020 wlisTvisac SenarCundeba (Dye et al., 1999, Smith & Frieden, 2004;
Dye et al., 2005). ufro metic, momdevno 20 wlis ganmavlobaSi tuberkuloziT
miliardi adamiani daavaddeba, xolo letalobis maCvenebeli 25 mln-mde
gaizrdeba. arsebuli mdgomareobiT, tuberkuloziT daavadebulTa 75%
ekonomikurad produqtiuli (15-54 wlis) asakobrivi jgufia, romelSic
sikvdilianobis maCvenebeli msoflio masStabiT 95%-s aRwevs, maqsimaluri
sixSiriT Sua saharis afrikaSi da samxreT-aRmosavleT aziaSi fiqsirdeba
(WHO, 2011; Tiemersma at al., 2011.).
tuberkulozis marTvis saqmeSi mniSvnelovan rols asrulebs diagnosti-
rebis meTodebis SerCeva. ganviTarebul qveynebSi am mizniT baqteriuli
kulturis meTodi (oqros standarti) da efeqturi sadiagnostiko
molekuluri testebi gamoiyeneba. CamorCenil da ganviTarebad qveynebSi
tuberkulozis gakontrolebis SesaZleblobas aferxebs diagnostirebis
moZvelebuli meTodebi, romelebic ver iZleva daavadebis zusti
identificirebis saSualebas. Sesabamisad, mkurnaloba araefeqturia, rac
sikvdilianobis maCveneblis zrdazec aisaxeba (Tiemersma at al., 2011). araswori
diagnostika da mkurnaloba mikobaqteriis rezistentuli Stamebis
gavrcelebis erT-erT mizezad iTvleba.
15
WHO-is mier xorcieldeba tuberkulozis epidemiologiis Seswavlis,
misi mimdinareobis Sefasebis, prevenciuli RonisZiebebis dagegmvisa da
ganxorcielebis globaluri kontroli. 2006 wlidan tuberkulozis
Sefasebis sami mTavari maCvenebeli gamoyeneba: axali SemTxveva
(mikobaqteriiT inficirebis axali SemTxvevebi), prevalentoba
(tuberkuloziT daavadebulTa ricxobrivi maCvenebeli konkretuli
periodisaTvis) da letaloba (tuberkuloziT gamowveuli sikvdilianoba
drois gansazRvrul periodSi, ZiriTadad, erTi wlis farglebSi). aRniSnul
maCveneblebze dayrdnobiT, axali ,,epidemiis’’ warmoSobis saSiSroebis gamo
tuberkulozi gamocxadda ,,globalur safrTxed’’, ris gamoc WHO
axorcielebs mizanmimarTul programebs „Stop TB Partnership - WHO Global Task
Force on TB Impact Measurement“-is farglebSi, raTa Semcirebuli iqnes zemoT
aRniSnuli maCveneblebi 2015 wlisTvis. programaSi CarTulni arian wamyvani
teqnikuri da finansuri partniorebi da tuberkulozis maRali maCveneblebis
mqone qveynebi (Palomino et al., 2007). tuberkulozis regionul doneze marTvis
saqmeSi aqtiurad gamoiyeneba 1994 wlidan WHO-s mier rekomendebuli pirdapiri
meTvalyureobiT mkurnalobis - DOTS strategia.
WHO-s mxardaWeriT ganxorcielebuli tuberkulozis kontrolis
Tanamedrove programebis Sedegebis mixedviT, 2006 wlidan rig qveynebSi
aRiniSna tuberkulozis axal SemTxvevaTa absoluturi ricxvis, xolo 2002
wlidan - misi sixSiris (yovel 100,000 individze) 1.3%-iT kleba. gamonakliss
warmoadgens afrikis regioni. partniorobis mizani faqtiurad miRweulia
amerikis da wynari okeanis dasavleT regionSi. daavadeba radikalurad
Semcirda CineTis regionSi (China Tuberculosis Control Collaboration, 1996).
aRsaniSnavia, rom 1990 wlis Semdeg letalobis maCvenebelic (aiv-dadebiTi
SemTxvevebis letaluri maCveneblis gamoricxviT) 1/3-T Semcirda da Tu
aRniSnuli tempi SenarCunebuli iqneba, „Stop TB Partnership’s“ mizani 2015 wlisTvis
50%-iT miRweulad CaiTvleba (WHO/HTM/TB/2010; WHO,2011). amavdroulad, WHO-
is monacemebiT jer kidev arsebobs qyveynebi, sadac axal SemTxvevaTa raodenoba
16
tuberkulozis prevalentobis 80% -s aRwevs. tuberkulozis axal SemTxvevaTa
raodenoba WHO-is 2010 wlis monacemebiT naCvenebia rukaze (sur.1).
tuberkulozis axal SemTxvevaTa, prevalentobis da letalobis
maCveneblebze gansakuTrebul gavlenas axdens: siRaribis zrda, demogra-
fiuli Zvrebi, paraleluri infeqciebi (pandemuri aiv) (Chretien et al, 1990;
Chintu et al, 2005) da aS. sagangebo mdgomareobas qmnis, aseve, mikobaqteriis
rezistentuli Stamebi (Haas et al., 1994; Fatkenheuer et al., 1999 Ballif et al., 2012).
daavadebis kontrolis organizaciebis Zalisxmevis, antituberkulo-
zuri programebis ganxorcielebis, mkurnalobis kombinirebuli meTodebis
gamoyenebis da maRalefeqturi medikamentebis xelmisawvdomobis miuxedavad,
tuberkulozi jer isev rCeba globalur safrTxed.
sur 1. tuberkulozis axal SemTxvevaTa gavrcelebis ruka msoflios masStabiT (WHO.2010). ferebiT naCvenebia tb-is axal SemTxvevaTa raodenoba yovel 100 000 mosaxleze
tuberkulozis epidemiologiur mdgomareobas gansakuTrebiT amwvavebs
ukanasknel aTwleulSi gazrdili multirezistentuli tuberkulozis
(MDR-TB) SemTxvevebi. 1994 wlidan rig qveynebSi tuberkulozuri pacientebis
17
5%-dan 19%-mde avaddeba axladSeZenili multirezistentuli mikobaqteriiT.
prevalentoba yovelwliurad 1.5 mln-s (60%) aRwevs (Zignol M, 2011).
I.2. tuberkulozis epidemiologia
saqarTveloSi
tuberkulozi saqarTveloSi, iseve, rogorc mTel msoflioSi,
sazogadoebis janmrTelobis sakmaod seriozuli da sayuradRebo problemaa.
sxva postsabWouri qveynebis msgavsad, saqarTvelo tuberkulozis pre-
valentobis maRali maCvenebliT gamoirCeva.
tuberkulozis pirveli kvali saqarTveloSi Cv.w.aR-is VI-VII saukuneebis
namarxebSia aRmoCenili. Zvel qarTul samedicino ZeglebSi tuberkulozi anu
„Wleqi" pirvelad X saukuneSi, kananelis "usworo karabadinSi", mogvianebiT ki
sxva Zvel qarTul samedicino xelnawerebSic gvxvdeba. aRniSnulma senma
saukuneebis ganmavlobaSi uamravi adamianis sicocxle imsxverpla.
tuberkulozTan brZolis pirveli mcdeloba qveyanaSi 1918-1921 ww.-Si
daiwyo, Seiqmna samedicino samecniero da kvleviTi centrebi. 1970-1990 ww.
tuberkulozis sawinaaRmdego RonisZiebebis gatarebis Sedegad, saqarTve-
los respublikaSi tuberkuloziT avadoba 56%-dan 28,3%-mde Semcirda,
xolo letaloba _ 10,9% dan 4,91%-mde.
1991-1994 ww.-Si saqarTveloSi mimdinare socialur-politikurma
movlenebma, jandacvis sistemis moSlam, samoqalaqo omma, afxazeTisa da
samxreT oseTis konfliqtebma, mosaxleobis mZime socialurma da ekonomi-
kurma pirobebma, aseve, msoflio masStabiT tuberkulozis epidemiologiuri
situaciis damZimebam gamoiwvia avadobis zrda da epidemiologiuri
mdgomareobis gauareseba. am periodSi tuberkulozTan brZolis Ronis-
Ziebebi praqtikulad ar xorcieldeboda, inerciiT grZeldeboda daavade-
18
bulTa usistemo diagnostika da mkurnaloba. yovelive amis Sedegad gaizar-
da daavadebiT gamowveuli sikvdilianobis da axal SemTxvevaTa sixSire.
USAID-is monacemebiT, tuberkulozis axal SemTxvevaTa da prevalen-
tobis maCveneblis sagrZnobi mateba saqarTveloSi 2001 - 2005 wlebSi
dafiqsirda. gansakuTrebiT maRali sixSiriT gamoirCeoda Sida qarTlis,
qvemo qarTlis, kaxeTis, aWaris, imereTis da samegrelos regionebi.
magaliTad, 2001 wels samegreloSi registrirebuli iyo 670 pacienti,
xolo 2005 wels maTi ricxvi 865-mde gaizarda. imereTSi 2001 wels
dafiqsirda 630, xolo 2005 wels _ 876 SemTxveva. aWaris regionSi xuTi
wlis ganmavlobaSi daavadebuli pacientebis raodenobam 496-dan 897-mde
moimata. aRniSnul periodSi gaizarda axali SemTxvevebis maCvenebelic.
magaliTad, aWaraSi 2001 wels tuberkulozis 364 axali SemTxveva
dafiqsirda, 2005 wels ki _ 614. 2005 wels saqarTvelos tuberkulozis
epidemiologiuri mdgomareoba TiTqmis utoldeboda maRali maCveneblis
mqone centraluri aziis regions (USAID, 2007).
2005 wlidan saqarTveloSi tuberkulozi SedarebiT ufro kotrolireba-
di gaxda, rasac xeli Seuwyo USAID-is da WHO-is mier ganxorcielebulma
programebma (mag., DOTS), romelTa strategiulma muSaobam met-naklebad
gaaumjobesa tuberkulozTan brZolis RonisZiebebi (Gegia M. et al. 2011).
sadReisod, daavadeba met-naklebad eqvemdebareba kontrols da tuberkulozis
prevalentobis maCvenebelic SedarebiT dastabilurebulia. aRniSnuli
mdgomareoba ar vrceldeba sapyrobileebze, sadac SeiniSneba daavadebis
sagangaSo zrda (Gegia M. et al. 2011).
saqarTvelos tuberkulozisa da filtvis daavadebaTa erovnuli
centridan mopovebul masalebze dayrdnobiT, tuberkulozis prevalentobisa
da axal SemTxvevaTa maCvenebeli populaciis ricxovnobasTan SefardebiT
2005-2010 wlebSi naCvenebia diagramebze (diagr. 1-2):
19
diagr. 1. saqarTvelos mosaxleobis ricxovnobis dinamika 1996-2010 wlebSi
diagr. 2. saqarTveloSi tuberkulozis prevalentobis da axal SemTxvevaTa maCvenebeli 1996-2010 wlebSi
mocemul statistikur monacemebze dayrdnobiT, SeiZleba iTqvas, rom
tuberkulozis prevalentoba saqarTveloSi maqsimaluri sixSiriT 2002-2005
ww. gamovlinda, xolo axal SemTxvevaTa mateba aRiniSna 2009-2010 wlebSi.
janmrTelobis globaluri marTvis organizaciis (Global Health Policy,
2011) monacemebiT, saqarTveloSi 2011 wlisaTvis dafiqsirda tuberkulozis
5400 axali SemTxveva, xolo daavadebis prevalentoba 6900-s Seadgenda, rom-
lis maCvenebeli yovel 100 000 mosaxleze, 159-is tolia. tuberkuloziT
5154497
4369500
43980004410900
4452800
3800000
4000000
4200000
4400000
4600000
4800000
5000000
5200000
5400000პოპულაც. რიცხ.
5887
3789 3117 3032
2826
3175 3230
9213
5019 5060
4546
4592 4526
0
2000
4000
6000
8000
10000
12000
14000
16000
პრევალენტობა ახალი შემთხვ.
20
gamowveuli sikvdilianobis maCvenebeli yovel 100 000 mosaxleze 160-s
Seadgens.
evropuli regionis masStabiT, saqarTvelo mexuTe qveyanaa
tuberkulozis prevalentobis maRali maCvenebliT da 27-ze maRali pre-
valentobis qveynebs Soris (Gegia et al., 2011). tuberkulozis kontrolis
gaZlierebis mizniT, 2012 wlis saxelmwifo programaSi, daavadebulTa mkur-
nalobis garda, gaTvaliswinebulia latenturi tuberkulozis mqone maRali
riskis jgufebis epidemiologiuri kvleva da mkurnaloba. saqarTveloSi
tuberkulozis diagnostika da mkurnaloba dReisaTvis ufaso da
xelmisawvdomia.
2012 wels daigegma tuberkulozis epidemiologiuri kvlevebis
gafarToveba, laboratoriuli diagnostikis xarisxis gaumjobeseba
da daavadebis droul gamovlenasa da mkurnalobis efeqturobaze mimarTuli
sxva RonisZiebebi, romelSic CarTulia tuberkulozisa da filtvis
daavadebaTa erovnuli centri da regionuli marTvis dawesebulebebi. Agarda
amisa, WHO rekomendaciiT, saqarTveloSi 1995 wlidan moqmedebs tuberkuloz-
Tan brZolis erovnuli programa, romlic efuZneba DOTS strategiebs.
ganxorcielebuli RonisZiebebis miuxedavad, daavadebis riskiT
saqarTvelo kvlav seriozuli safrTxis winaSe mdgom ganviTarebad qveynebs
Soris moiazreba. amis erT-erTi mTavari mizezi wamalrezistentuli formis
tuberkulozis sagrZnoblad gazrdili maCvenebelia, romelsac sxvadasxva
tipis medikamentisadmi gamZle mikobaqteriebi iwvevs. magaliTad, 2005 wels
94 axali SemTxvevidan (100 000 mosaxleze) multirezistentuli tuberkulo-
zis 6,8% pirveladi rezistentobis, xolo 27,4% warsulSi namkurnalevi
SemTxvevebi Seadgenda (Mdivani et al, 2009; Gegia et al, 2011).
gansakuTrebul safrTxes sazogadoebaSi mikobaqteriis rezistentuli
Stamebis gavrceleba qmnis. aseTi StamiT inficirebis SemTxvevaSi pacienti
pirdapir rezistentuli tuberkuloziT xdeba avad. rogorc me-3
diagramidan Cans, saqarTvelos tuberkulozisa da filtvis daavadebaTa
21
erovnuli centris monacemebiT, 2009-2010 ww.-Si mkveTrad moimata pirveladi
rezistentobis axal SemTxvevaTa raodenobam.
diagr. 3. saqarTveloSi rezistentuli tuberkulozis axal da namkurnalev SemTxvevaTa
maCvenebeli 2006-2010 wlebSi (saqarTvelos tuberkulozisa da filtvis daavadebaTa
erovnuli centri)
mdgomareobas amZimebs is faqti, rom pirveladi rezistentobis dros
mikobaqteriebis Stamebi gansxvavebul mdgradobas avlenen sxvadasxva
antituberkulozuri medikamentis mimarT, rac kidev ufro arTulebs
samkurnalo preparatebis efeqturobas rezistentuli tuberkulozis
srulyofili mkurnalobisTvis.
I .3. tuberkulozis gamomwvevi -Mycobacterium tuberculosis
M. tuberculosis da masTan monaTesave koloniebi warmoiSva ramdenime aTeuli
aTasi wlis win aRmosavleT afrikaSi da SemdgomSi evoluciurad gamoeyo Tavis
winapar saxeobas da Camoyalibda, rogorc M. tuberculosis kolonia. M. tuberculosis -
is winaprebi 3 mln wlisaa (Gutierrez et al., 2005).
0 20 40 60 80 100 120 140
2006
2007
2008
2009
2010
43,3
21,9
54,4
87,8
88,6
28,8
12,4
31,4
33,8
33,3
ახალი შემთხ. % ნამკურნ. %
22
mikobaqteriebis umravlesoba aratuberkulozuri anu atipuri,
arapaTogenuri mikobaqteriebia. maTi ramdenime saxeoba adamianisa da
cxovelebis ujredSida paTogenia (M. tuberculosis, M. canettii M. africanum, da M. bovis,
M. Microti). M. tuberkulosis, M. africanum da M. bovis mikobaqteriebi cnobilia,
rogorc ,,tuberkulozis kompleqsi’’, romlis TiToeuli wevri paTogenuria
da iwvevs daavadebas. M.africanum-is Stami ZiriTadad dasavleT afrikaSi
gvxvdeba. M.bovis tuberkulozis ganviTarebas iwvevs Sinaur da gareul
msxvilfexa saqonelSi. iSviaTad, auduRari an arapasterizebuli rZis
miRebis Sedegad is SeiZleba adamiansac gadaeces. aRniSnuli saxeoba,
savaraudod, M. tuberculosis winaparia. varaudoben, rom am gziT pirvelad indo-
evropelebi dainficirdnen, aqedan daavadeba dasavleT evropasa da aziaSi
gadavida, xolo Cv.w.aR-mde 1000 wlisTvis mTels msoflioSi gavrcelda.
M. Tuberculosis 1,5–6mkm sigrZis da 0,2–0,5mkm sisqis moxrili formis
baqteriaa, romelic paTologiur masalaSi grovebs qmnis. igi daculia
unikaluri, lipidebiT mdidari ujreduli kedliT, romelSic uxvadaa
cximovani mJavebi da glikolipidebi, rac gamoSrobisa da qimiuri agentebis
moqmedebisgan icavs. msgavsi Sedgenlobis membrana bacilas saSualebas
aZlevs, antimikrobuli damcvelobiTi meqanizmebis moqmedebisagan Tavi
gadairCinos da recipient organizmSi gamravldes (Hingley-Wilson et al, 2003;
Zahrt,2003; Rom & Garay, 2003; Rom & Garay, 2004). M. tuberculosis gram-rezistentuli
aerobia da Zalian nela izrdeba (maTi ricxvis gaormagebas saSualod 20 sT
sWirdeba). filtvebis bneli, JangbadiT mdidari are da 37°C temperatura
bacilis gamravlebisaTvis idealuri garemoa. igi swrafad iSleba
ultraiisferi sxivebis zemoqmedebiT, magram mdgradia sxvadasxva fizikuri
da qimiuri agentebisadmi. baqteria 5–6 Tvis ganmavlobaSi inarCunebs sico-
cxlisunarianobas Txevad naxvelSi. aseve, ramdenime Tvis ganmavlobaSi
sicoclisunariani rCeba gamomSral mdgomareobaSi da inarCunebs
virulentobas. xelsayrel garemo pirobebSi moxvedrisas avlens paTogenur
aqtivobas.
23
M.tuberculosis, Cveulebriv, azianebs filtvebs (filtvis tuberkulozi) da
sxva organoebs (filtvgare tuberkulozi _ Tavis tvinis garsebi, Zvlebi,
saxsrebi, Tirkmlebi, Sardis buSti). daavadeba kontagiozuria.
M.tuberculosis-iT inficirebulTa 90% SemTxvevaSi baqteria rCeba latentur
fazaSi, mxolod 10%-Si aRiniSneba daavadebis klinikuri ganviTareba.
pirveladi inficirebis Sedegad yalibdeba nawilobrivi imuniteti, Tumca,
masiuri infeqciis an imunosupresiis arsebobis pirobebSi imuniteti ver
uzrunvelyofs daavadebis prevencias da igi gadadis aqtiur fazaSi. pirvelad
tuberkulozur keraSi arsebuli mikobaqteriebi iwyeben intensiur
gamravlebas, kera moculobaSi matulobs, SeiZleba SemdgomSi qsovili
dairRves da daSlili qsovilis adgilze Camoyalibdes Rru. pirveladi keridan
mikobaqteriebi sisxlis nakadis meSveobiT SeiZleba moxvdnen sxvadasxva
organoSi, sadac, aseve, viTardeba tuberkulozuri procesi (Kochar et.al., 2011).
daavadebis Ria formis (mgb+) dros avadmyofi xvelis, ceminebis an saubris
dros saSualod 10-15 adamians ainficirebs. janmrTeli adamianis imunuri
sistema, an xocavs tuberkulozis bacilebs, an "akonservebs" wlebis ganmavlo-
baSi (Kochar et.al. 2011).
tuberkulozis mimarT mRali riskis qveS arian daavadebulTa ojaxis
wevrebi, Raribi, usaxlkaro, saerTo sacxovreblebSi mcxovrebni, gansa-
kuTrebiT - patimrebi; paraleluri daavadebebis (simsivne, diabeti, Sidsi)
mqoneni, eqimebi da jandacvis sxva momsaxure personali; aseve, adamianebi,
romlebic infeqciuri daavadebebisadmi maRali mgrZnobelobis imunogeneti-
kur faqtorebs atareben.
daavadebis mkurnaloba sakmaod xangrZlivi da rTuli procesia. Tu
mkurnaloba uwyvetad da, amasTanave, erTdroulad ramdenime antituber-
kulozuri preparatiT mimdinareobs, SesaZlebelia pirveladi tuberkuloziT
daavadebuli TiTqmis yvela pacientis gamojanmrTeleba. Sewyvetili
mkurnaloba, xSirad, infeqciis recidiul formas iwvevs da
antituberkulozuri medikamentebis mimarT rezistentobis Camoyalibebas
24
ganapirobebs, rac arc Tu iSviaTad ukontrolo procesebSi gadadis da
letaluri SedegiT sruldeba.
1.3.1. mikobaqteriis rezistentobis ganmapirobebeli faqtorebi
antibiotikebiT tuberkulozis arasaTanado mkurnalobis an misi
Sewyvetisas mikobaqteriaSi momxdari genuri mutaciebi, xSirad, sxvadasxva
saxis medikamentisadmi rezistentobas iwvevs. konkretuli wamlis mimarT
rezistentobas metwilad baqteriaSi momxdari spontanuri mutaciebi
ganapirobebs, romelTa sixSire 10-6-dan 10-8-mde meryeobs romelime erTi
wamlis mimarT, xolo erTze meti wamlis mimarT rezistntobisas mutaciaTa
sixSire 1012-1016 mikrobul ujreds Seadgens (Palomino et al., 2007). Mutaciebi,
SesaZloa, gamowveuli iyos replikaciis dros momxdari genetikuri
struqturis iseTi cvlilebiT, romlis gavleniT baqteriam SeiZleba
dakargos adekvaturoba antituberkulozuri medikamentis mimarT.
mikobaqteriis populaciaSi mudmivad mimdinare transmisiebi rezistentobis
Camoyalibebis mniSvnelovani wyaro xdeba (Bartu et al., 2007).
rezistentobis gamomwvevi klasikuri meqanizmis mixedviT, mutacia xdeba
mikobaqteriis genis im nawilSi, romelic akodirebs wamlis samizne
ligandebs. mutacia axdens im fermentebis inhibirebas, romlebic
pasuxismgebelia wamlis samizne receptorebis Camoyalibebaze. faqtobrivad,
aRniSnuli mutaciebi amcirebs wamlis SesaZleblobas, ipovos da
daukavSirdes samizneebs mikobaqteriaSi.
sxva tipis mutaciebis dros ki, piriqiT, matulobs wamlis samizne
ligandebi. baqteriis zedapirze yalibdeba ufro meti ligandi, vidre es
wamliTaa SesaZlebeli. zogierTi medikamenti, magaliTad, izoniazidi (INH)
da pirazinamidi (PZA) baqteriis ujredSi Sedis, rogorc prowamali, romelsac
gaaqtiurebisTvis sWirdeba baqteriuli fermenti. aqedan gamomdinare, nebis-
25
mieri mutacia, romelic Trgunavs aRniSnuli fermentis sinTezs, TavisTavad
blokavs wamlis aqtivobas da saboloo jamSi yalibdeba rezistentoba.
mikobaqteriis rezistentobis mizezi SesaZloa iyos iseTi tipis
mutaciebic, romlebic amcireben wamlis akumulacias baqteriis SigniT. es
SesaZlebelia baqteriaSi wamlis ganvladobis SemcirebiT an baqteriidan misi
gamosvlis aCqarebiT. sabolood, rezistentoba SeiZleba preparatis qimiuri
modificirebiT da inaqtivirebiT ganviTardes (Bastian & Portales, 2000).
poli- da multirezistentobis gamomwvevi mutaciebi xdeba ara erT
romelime genur lokusSi, aramed _ ramdenimeSi erTad.
amJamad cnobilia rezistentobis ganmapirobebeli mutaciuri saitebi.
magaliTad, rpsL (STM-streptomicinis samizne) rpoB (RIF-rifampicinis samizne)
an 16S ribosomul rnm-Si (KAN kanamicinis, AMK amikacinis da 2-deoqsistrep-
tamin aminoglikozidebis samizne) momxdari mutaciebi asocirdeba
rezistentobis maRal donesTan, xolo gldB (STM-streptomicinis samizne) eis
(KAN kanamicinis samizne) da inhA (INH izoniazidis samizne) genebSi momxdari
mutaciebi asocirdeba rezistentobis SedarebiT dabal donesTan. zogjer,
erTi wamlis mimarT rezistentoba, SesaZloa, gamowveuli iyos mravali
genis erToblivi gardaqmnebiT an kidev piriqiT, SesaZloa, erTi da igive
genis sxvadasxva lokusSi momxdari mravlobiTi gardaqmnebiT (Bottger, 2011).
molekulur doneze mutaciebis dadgenas specialuri teqnikis
gamoyenebiT axdenen. es meTodebi sakmaod sensitiuri, specifikuri da swra-
fia da misi saSualebiT SesaZlebelia Canacvlebuli iqnes baqteriologiu-
ri testirebis meTodi. amavdroulad, testis saimedoobas mutaciis identifika-
ciis sizustec ganapirobebs (Lee et al., 2000; Goh et al., 2006; Bottger, 2011).
rezistentoba, SesaZloa, iyos bunebrivi anu pirveladi an SeZenili anu
meoradi, rac metwilad pacientis anamneziT dgindeba. SeZenil da bunebriv
rezistentobebs Soris Tanafardoba araTanabaria (Bastain & Portales, 2000).
rezistentobis ganviTarebis Tavidan acilebis saukeTeso gza kargad dagegmili
26
pirveli rigis mkurnalobaa. aseve, mniSvnelovania profilaqtikuri
RonisZiebebis gatareba tuberkulozisadmi maRali riskis jgufebSi.
I .4. rezistentuli tuberkulozis globaluri
epidemiologia da etiologia
antituberkulozuri medikamentebis mimarT rezistentoba dokumenturad
1940 wlidan dafiqsirda, xolo problemis monitoringi mxolod 1994
wlidan daiwyo, rodesac rezistentobis problemam globaluri saxe miiRo.
ukanaskneli aTwleulis ganmavlobaSi msoflioSi tuberkulozis epidemio-
logiuri situaciis gauareseba, garkveulwilad, wamalrezistentuli
formis gavrcelebas ukavSirdeba. daavadebam samxreT afrikaSi ifeTqa aiv-is
virusis fonze, ramac mniSvnelovnad gazarda sikvdilianobis maCvenebeli
(Zignol et al, 2011).
wamalrezistentuli tuberkulozis (DR-TB) gamomwvevia M. tuberculosis,
romelic mdgradia tubsawinaaRmdego medikamentebis mimarT. imisda mixedviT,
Tu romeli rigis da ra tipis wamlebis mimarTaa mikobaqteria rezistentuli,
gamoyofen tuberkulozis mono-, poli- da multirezistentul formebs.
tuberkulozis samkurnalod gamoiyeneba I rigis (eTanbutoli (EMB/E,
izoniazidi (INH/ H), pirazinamidi (PZA/Z)) da II rigis wamlebi (aminoglikozi-
debi: amikacini (AMK), kanamicini (KM); polipeptidebi: kapreomicini, viomicini,
enviomicini; fluoroqinolebi: ciprofloqsacini (CIP), levofloqsacini
(MXF); Tioamidebi: eTionamidi, proTionamidi).
roca mikobaqteria gamZlea ori an meti tubsawinaaRmdego medikamentis
mimarT, magram ara erTdroulad izoniazidis da rifampicinis mimarT,
polirezistentul tuberkulozad (PDR-TB) iwodeba. multirezistentuli
tuberkulozis (MDR-TB) _ daavadebis gamomwvevi mikobaqteria gamZlea, minimum,
izoniazidis da rifampicinis mimarT. Tu pacienti rezistentulia pirveli
27
rigis wamlebis mimarT, maT mkurnaloben meore rigis wamlebiT, romlebic
sakmaod ZviradRirebulia, axasiaTebs gacilebiT meti gverdiTi efeqti da
moiTxovs xangrZliv mkurnalobas. rezistentuli tuberkulozis umZimesi
formaa eqstensiuri tuberkulozi (XDR-TB), romlis gamomwvevi mikobaqteria
gamZlea izoniazidinis da rifampicinis, fluoroqinolebis jgufis
medikamentebis da, Tundac, erTi saineqcio medikamentebis (kanamicini, amikacini,
kapreomicini) mimarT (Floyd., 2003; Smith., 2003; WHO, 2005).
medikamentebisadmi rezistentoba SeiZleba bunebrivi an SeZenili iyos.
mutaciebi, romlebic iwvevs bunebriv rezistentobas, oTxive pirveli rigis
tubsawinaaRmdego medikamentis mimarT, gansazRvruli albaTobiT xdeba
aranamkurnalev adamianebSi H–10-6; S–10-6; E–10-6; R–10-8. xolo ori damoukidebeli
medikamentis mimarT rezistentobis ganviTarebis albaToba, magaliTad, H+R
SemTxvevaSi Seadgens 10-6 X 10-8=10-14. imis gamo, rom baqteriebis raodenoba,
mZime kavernozuli formis drosac ki iSviaTad aRwevs 10-14
multirezistentuli baqteriis spontanuri evolucia Zalian iSviaTia.
SeZenili (meoradi) rezistentoba viTardeba tuberkulozis mkurnalobisas,
roca mkurnalobis zemoqmedebiT xdeba baqteriebis mutanturi formebis
seleqcia (Long, 2000). rezistentobis xSiri mizezia mkurnalobaze pacientis
cudi damyoloba an arasrulfasovani reJimi (gaidlaini, 2007).
multirezistentoba seriozuli problemaa aRmosavleT evropis, aziisa da
afrikis qveynebisTvis. WHO-s monacemebiT, rezistentuli tuberkuloziT 2008
wels gardaicvala 150 000 adamiani. 2010 wlisTvis multirezistentuli
tuberkulozis 650 000 axali SemTxveva dafiqsirda (WHO 2011/2012).
varaudeben, rom multirezistentuli tuberkuloziT gamowveuli
letalobis maCvenebeli gacilebiT maRalia, vidre es oficialurad aris
cnobili. statistikuri monacemebis sizustes eWvqveS ayenebs is faqti, rom
tuberkulozuri pacientebis Zalian did nawils ara aqvs diagnozis sworad
28
dasmis SesaZlebloba Tanamedrove sadiagnostiko laboratoriebis ararse-
bobis an arasakmarisobis gamo (Bastain & Portales, 2000; Zignol et al, 2011).
rezistentuli tuberkulozis problema mwvaved dgas saqarTveloSic.
qveyanaSi multirezistentuli tuberkulozis maCvenebelma 1995-1996 wlebSi
axal SemTxvevaTa 23-25%-s miaRwia, xolo namkurnalev SemTxvevebSi _ 39%-s.
2003 wlis monacemebiT, axal SemTxvevaTa 15%-Si da namkurnalevi
SemTxvevebis 23%-Si dafiqsirda daavadebis multirezistentuli forma
(Zalesky et, al., 1999). 2005 wels yovel 100 000 mosaxleze dafiqsirda
tuberkulozis 94 SemTxveva, sadac axali SemTxvevebis 6.8% da warsulSi
namkurnalevi SemTxvevebis 27.4% multirezistentul tuberkulozze modioda
(gaidlaini, 2007). 2009 wels multirezistentuli formam tuberkulozis
prevalentobis saerTo maCveneblis 28,1% Seadgina, romlis 10,5% pirvelad
rezistentobaze modis, 53,1% ki _ namkurnalev SemTxvevebze (Mdivani et al.,2009).
rezistentuli Stamebis farTod gavrcelebis saSiSroeba msoflioSi
moiTxovs tuberkulozis damatebiTi kontrolis meqanizmebis amoqmedebas,
diagnostirebis axali meTodebis Seqmnas da danergvas, arsebuli
antituberkulozuri medikamentebis gaumjobesebas (Palomino et al., 2007).
1.5. multifaqtoruli daavadebebi da
populaciebis genetikuri polimorfizmi
evoluciuri ganviTarebis procesSi adamianTa populaciebi sxvadasxva
faqtoris zemoqmedebis qveS, garkveulwilad, „genetikurad erTmaneTs
emijnebodnen“ da iZendnen individualobas. amavdroulad, maT Soris mudmivad
mimdinareobda genebis gacvla, rac Tavis mxriv, saerTo genetikuri niSnebis
Camoyalibebas uwyobda xels. adamiani, rogorc biologiuri saxeoba, imdenad
29
axalgazrdaa, rom arc erT mis populacias ar gaaCnia drois iseTi maragi, rac
maT srul izolacias uzrunvelyofda (Степанов, 2010).
eTnikuri populaciebis genofondi masSi Semavali genebis doneze inaxavs
informacias yvela im mniSvnelovani procesis Sesaxeb, romlebic eTnosma
istoriuli ganviTarebis procesSi gadaitana (Cavalli-Sforza., 1998). populaciis
genofondSi genebis da maTi alelebis mravalferovneba populaciur
polimorfizms qmnis. polimorfuli variaciebis (geno- Tu fenotipuri)
wonasworoba, romelic Camoyalibda genTa nakadebisa da bunebrivi gadarCevis
moqmedebiT, individualobas sZens yovel populacias.
populaciaTa polimorfizmis individualoba xSirad daavadebaTa mimarT
gansxvavebul mgrZnobelobaSi vlindeba (Conrad et al., 2010). arsebobs
populaciebi, romlebic metad eqvemdebarebian romelime konkretul daavadebas,
maSin, roca sxvebi mis mimarT mdgradobiT gamoirCevian. es faqti gansakuTrebiT
kargad Cans multifaqtorul daavadebebTan mimarTebaSi (diasamiZe, 2008; Conrad
et al., 2010). daavadebaTa mimarT populaciebis gansxvavebuli mgrZnobeloba
zogjer populaciaTa lokaluri adaptaciebiTac aixsneba (Cheboksari et al., 2006).
cnobilia, rom xSirad daavadebisadmi mdgradoba Tu sensibiloba
damokidebulia genomSi ara erTi romelime konkretuli genis arsebobaze,
aramed - ramdenimeze erTad. daavadebaTa mravali faqtoriT ganpirobebulobis
gamo, maT mimarT memkvidruli midrekileba maRali variabelobiT xasiaTdeba
da igi pirdapir kavSirSia populaciuri polimorfizmis siZlieresTan
(Степанов, 2010). mfd-sadmi populaciaTa gansxvavebuli midrekileba naCvenebia
gul-sisxlZarRvTa daavadebebis (Voevoda et al., 2006; Wassel et al.,2009), diabetis
(Karter et al., 2002), zogierTi tipis simsivnis (Shibata et al., 1997), glaukomis (Tielsch et
al.,1991), nefropaTiebis (Tarver-Carr et al., 2002) da mravali sxva daavadebis
mimarT.
TiTqmis saukunea, rac aRiarebulia, rom tuberkulozis mimarT
mgrZnobeloba gansxvavebulia, rogorc rasebis, aseve populaciebis doneze
30
(Millar, 1908). mecnierebi miiCneven, rom populaciis mdgradoba tuberkulozis
mimarT ganisazRvreba populaciis „klinikuri“ istoriiT (Stead., 1992). zogadad,
msoflios Savkaniani populacia tuberkulozisadmi maRali mgrZnobelobiT
gamoirCeva, vidre evropelebi, rac SesaZloa, aixsnas imiT, rom evropis
regionisTvis tuberkulozi endemuria da bevrad didi xnis istoria aqvs,
rogorc gadamrCev evoluciur faqtors (Dubos & Dubos, 1952), xolo Savkanian
mosaxleobaSi daavadebis (gansakuTrebiT daavadebis mZime formebis) maRali
sixSire tuberkulozis mimarT aRniSnuli rasis maRal mgrZnobelobaze
miuTiTebs (Bellamy et al.,1998). samedicino sferos warmomadgenlebis azriT,
tuberkulozis mimarT rasobrivi gansxvavebebi garemo faqtorebiT
ganisazRvreba, magram mravali faqti adasturebs daavadebisadmi genetikur
winaswarganpirobebulobasac. stidisa da misi TanamSromlebis (Stead et al.,
1990) mier dafiqsirda, rom saerTo sacxovreblis 25000 tuberkulin-
uaryofiT mobinadres Soris Savkanianebi orjer meti sixSiriT
dainficirdnen tuberkuloziT, vidre TeTrkanianebi, romlebic igive
garemoSi cxovrobdnen. aRniSnuli faqti aSkarad metyvelebs, rom tuber-
kulozisadmi organizmis mgrZnobelobaze genetikur faqtorebs garkveuli
roli akisriaT.
daavadebaTa mimarT populaciebis gansxvavebuli mgrZnobeloba
(midrekileba Tu mdgradoba) garkveulwilad alelTa garemocvazec aris
damokidebuli. aqedan gamomdinare, daavadebebis mimarT populaciis memkvidrul
winaswarganpirobebulobas populaciis mTliani genetikuri struqtura
gansazRvravs (Cavalli-Sforza, 1998; Степанов, 2010).
eTno-genetikuri divergenciis da mravalferovnebis msgavseba- gansxvavebis
Seswavla eTnikur jgufebSi da populaciebSi 1950 wlidan daiwyo cilovani
markerebis gamoyenebiT (Cavalli-Sforza, 1971; Mourant et al., 1976). mogvianebiT am
mizniT genetikuri markerebis gamoyeneba daiwyes. dagrovili faqtobrivi
masalis safuZvelze eTnogenetika calke mimarTulebad Camoyalibda (Underhill et
al., 2000). ukanasknel wlebSi ki populaciebis variabelobis Seswavla da
31
daavadebebTan maTi asociaciuri kavSirebis gamovlena dnm-is erTnukleo-
tidiani cvlilebebis polimorfizmis (SNP) doneze xdeba. Tanamedrove teqnika,
aseve, saSualebas iZleva genomis seqvenirebis safuZvelze GWAS-meTodiT
Seswavlil iqnes mTeli populaciis genofondi (Novembre et al., 2008; Auton et al.,
2009).
adamianis populaciebs Soris genetikuri gansxvaveba genetikuri
variabelobis mxolod 10-15%-s Seadgens. misi Seswavla personalizebul
medicinaSi monogenuri daavadebebis diagnostirebis saukeTeso saSualebaa,
xolo mfd-sas saSualebas iZleva, gamovlenili iqnes daavadebisadmi
winaswarganpirobebulobis faqtorebi. ukanaskneli daavadebis winaswari
prognozirebis da efeqturi Terapiis saSualebas iZleva (Степанов, 2010).
udavoa, rom eTnikuri faqtori unda iqnes gaTvaliswinebuli samedicino
kvlevebSi, gansakuTrebiT ki personalizebul medicinaSi (Genet. Hum. Race, 2004).
mkvlevarebi, romlebic muSaoben personalur genomikaSi, seriozul
yuradRebas uTmoben populaciur aspeqtebs. monacemTa Segrovebis da
damuSavebisas monacemebis interpretacias individualur an populaciur
doneze axdenen (Khoury et al., 2009).
iseve, rogorc yovel populacias aqvs Tavisi genofondi, yovel
individs gaaCnia Tavisi individualuri genotipi. genomSi arsebuli
TiToeuli geni pasuxismgebelia organizmis gansazRvrul niSan–Tvisebaze,
maT Soris daavadebebis mimarT organizmis mgrZnobelobaze. geografiuli
regioni, eTnikuri jgufi da populacia mniSvnelovnad gansazRvravs
individis aRniSnul maxasiaTeblebs (Cavalli-Sforza, 1998). cnobilia, rom bevri
infeqciuri paTogenis gamovlenis xarisxze imunogenetikuri lokusebi axdens
gavlenas.
mikobaqteriis aqtivacias da tuberkulozis klinikur ganviTarebas iwvevs
organizmis imunuri sistemis daqveiTeba, romelic ganpirobebulia rogorc
garemo (Holmes et al.,1998; Davies,1999; Schwenk & Macallan. 2000), ise genetikuri
(genebi, alelebi, haplotipebi) faqtorebiT, rac tyupebis Seswavlis klasikuri
32
meTodebiT gamovlinda. jer kidev gasul saukuneSi Catarebuli kvlevebiT
monozigotur tyupebSi daavadebisadmi maRali konkordantoba dafiqsirda
dizigoturebTan SedarebiT, rac imaze miuTiTebs, rom eTnikuri jgufebis
SigniT (individebis doneze) genetikuri faqtorebi gavlenas axdens
tuberkulozisadmi winaswarganpirobebulobaze (Comstock, 1978).
daavadebaTa mimarT organizmis midrekileba an mdgradoba xSir
SemTxvevaSi fenotipur niSnebiTanaa dakavSirebuli. erT-erT aseT
fenotipur niSans warmoadgens eriTrocituri jgufuri antigenebi,
romlebic ganlagebulia eriTrocitebis membranaze da gansazRvraven
pirovnebis individualobas da xSirad daavadebebisadmi asociacias avlenen
(Tamaria et al, 2010).
I.5.1 eriTrocituri jgufuri antigenebi da maTi
asociaciuri kavSirebi sxvadasxva tipis paTologiebTan da
tuberkulozTan
eriTrocituri jgufuri antigenebi da maT mier gansazRvruli sisxlis
jgufebi genetikurad myarad determinirebul fenotipur niSans warmoadgens
(Донсков, 2001). mravali mecnieruli kvleva adasturebs, rom arsebobs
korelaciuri kavSirebi sxvadasxva tipis infeqciur Tu arainfeqciur
daavadebasa da eriTrocitur jgufur antigenebs da, Sesabamisad, sisxlis
fenotipur jgufebs Soris. dRes ukve cnobilia, Tu romeli daavadebisken
arian midrekilni sisxlis pirveli jgufis adamianebi meoresTan SedarebiT
da a.S.
АВ0 sistemis antigenebi, maTi gavrceleba da asociacia daavadebebTan.
ABO sistema xasiaTdeba eriTrocitis zedapirze sami ZiriTadi antigenis - А, В,
H da plazmaSi - bunebrivi jgufspecifikuri glikoproteinuli anti -А da anti
- В antisxeulebis arsebobiT (Ogasawara et al., 1996). isini eriTrocitebis garda,
aRmoCenilia agreTve sekretebSi da adamianis qsovilTa umravlesobaSi
33
(Головачев, 1983). АВH antigenebi napovnia, aseve, sisxlSi leikocitebisa da
Trombocitebis membranis zedapirze (Доссе, 1959). АВ0 sistemis genuri lokusi
moTavsebulia me-9 qromosomaSi -9 q 34.1-q34.2. H genuri lokusi, romelic H
nivTierebis sinTezs akontrolebs, moTavsebulia 19 q13.3. igi АВ0-sgan
damoukidebel antigenur sistemas warmoadgens (Reguigne-Arnould et al., 1995;
Schenkel-Brunner, 2000).
sisxlis ABO sistemis fenotipuri jgufebis sixSire araTanabaria
msoflios populaciebSi, rac damokidebulia 0, А da В alelebis
ganawilebaze. eriTrocituri jgufuri antigenebis gavrcelebis variabe-
loba gamowveulia wlebis win populaciebis migraciebiTa da maTi SereviT.
aseve, populaciebis klinikuri istoriiT (gadatanili daavadebebi), re-
produqciuli TaviseburebiT da wes-CveulebiT, geografiuli arealiT,
genetikuri TaviseburebiT da a.S. mogvianebiT populaciebSi moxda maTi
dabalanseba da dafiqsireba, rogorc populaciisTvis damaxasiaTebeli
myari genetikuri niSani (Nasidze, 1995; Kucher at al., 2000; Михайлова c соавт., 2002;
Varsahr at al., 2003; Schmidt & Scheil, 2003).
msoflioSi yvelaze maRali sixSiriT (63%) O fenotipuri jgufia
gavrcelebuli. centralur da samxreT amerikis mkvidr populaciaSi misi
gavrceleba TiTqmis 100%-ia. aseve, maRalia misi sixSire avstraliel
aborigenebSi da dasavleT evropaSi. yvelaze dabali sixSiriT aRniSnuli
fenotipuri fgufi aRmosavleT evropasa da centralur aziaSia warmodgenili
(Garratty et al., 2004; Daniels et al, 2004; Dean 2005).
A aleli SedarebiT ufro farTodaa gavrcelebuli (21%) msoflios
mosaxleobaSi, vidre B. misi yvelaze maRali koncentracia montanas Savkanian
indielebSi (80%), avstraliel aborigenebSi (40-53%) da Crdilo skandinaviis
qveynebSi (laplandia, saamis qyveynebi) (50-90%) fiqsirdeba. aRniSnuli aleli
TiTqmis ar gvxvdeba centralur da samxreT amerikis indielebSi (Dean, 2005).
B(III) fenotipuri jgufi SedarebiT iSviaTi gavrcelebiT xasiaTdeba. B
alels msoflio mosaxleobis mxolod 16% atarebs. SedarebiT maRali
34
sixSiriT fiqsirdeba igi centralur aziasa da afrikaSi. Zalian dabalia misi
gavrcelebis sixSire amerikisa da avstraliis aborigenul mosaxleobaSi
(Garratty et al., 2004; Dean, 2005).
AB iSviaTi fenotipuri jgufia. maqsimaluri sixSiriT (10%) igi CinelebSi
da koreelebSi gvxvdeba (Dean, 2005).
evropelebSi ABO sistemis fenotipuri jgufebi Semdegi TanafardobiT
nawildeba: O-44%; A1-33%, A2-10%; B-9%; A1B,-3%, A2B-1% (Dean, 2005).
saqarTveloSi ABO sistemis fenotipebis gavrcelebiT pirvel adgilzea
sisxlis O fenotipuri jgufi, meore adgils ikavebs A fenotipuri jgufi,
mesames B, xolo yvelaze dabali sixSiriT AB jgufi fiqsirdeba (Арчвадзе, 1978).
ukanaskneli monacemebiT, aWaris regionSi ABO sistemis fenotipuri jgufebis
gavrceleba Semdeg suraTs iZleva: O fenotipuri jgufi 47,6±3%; A _ 36±5,1%; B –
11,4±3,5%; AB _ 4,2±2% (Nagervadze et al., 2010). aRniSnuli sistemis alelebidan
yvelaze maRali (0,68) sixSiriT O alelia warmodgenili. rac Seexeba A alels,
misi sixSire 0,23-s, xolo B alelis - 0,09-s utoldeba (Nagervadze et al, 2010).
ramdenadac, yvela aloantigeni Sesabamisi genis serologiur produqts
warmoadgens da met-naklebad CarTulia organizmis imunur SesaZ-
leblobebSi, amdenad, sakmaod zustad SeiZleba korelaciuri kavSiris
Seswavla antigenur Semadgenlobasa da sxvadasxva saxis paTologias Soris.
dRes TiTqmis srulyofiladaa Seswavlili ABO sistemis sisxlis
jgufuri antigenebis klinikuri mniSvneloba da maTi roli transfuzi-
ologiaSi, magram aRniSnuli sistemis daavadebebTan asociaciuri kavSirebis
Seswavla, jer kidev, mecnieruli kvlevebis interesis sferod rCeba.
sisxlis jgufebsa da sxvadasxva saxis paTologiebs Soris
asociaciuri kavSirebis Sesaxeb literaturaSi monacemebi mravlad
moipoveba, romelic xSirad populaciebis Taviseburebebze aisaxeba.
infeqciuri daavadebebi yovelTvis mniSvnelovan rols TamaSobda
populaciebis genetikuri struqturis cvlilebaSi. cnobilia, rom popula-
ciebSi АВ0 sistemis antigenebis gavrcelebis sixSire pirdapir kavSirSia
35
aRniSnuli populaciis klinikur warsulTan, kerZod, iseT epidemiur,
infeqciur daavadebebTan, rogoricaa: Savi Wiri, qolera, yvavili, malaria.
im regionebSi, sadac gasul saukuneSi aRniSnuli epidemiebi mZvinvarebda,
gamoikveTa АВ0 sistemis р alelis sixSiris kleba, xolo q alelis sixSiris
zrda. swored, daavadebebis kerebTan alelTa sixSiris damokidebulebiT
aixsneba 0(I) da B(III) jgufis warmomadgenlebis simcire mongoloidur
populaciebSi, xolo A(II)-jgufis – evropoidul populaciebSi da a. S. (Salmon,
1979; Прокоп и Геллер., 1991).
gasuli saukunis 90-ian wlebSi ganxorcielebuli mecnieruli kvlevebiT
dadgenili iqna, rom mniSvnelovani asociaciebi arsebobs АВ0 fenotipur
jgufebsa da ama Tu im saxis paTologias Soris (Markovic et al., 1991; Nazaretian et
al., 1993; Albarus et al., 1997; Vojvodic, 2000). zogjer ABO sistemis fenotipebsa da
daavadebebs Soris imdenad myari korelacia ikveTeba, rom xSirad ama Tu im
fenotipuri jgufis matarebloba romelime konkretuli daavadebis mimarT
midrekilebas gansazRvravs.
ABO sistemis antigenebi korelaciaSia kuWis wylulovan da simsivnur
daavadebebTan (Dean, 2005). amas adasturebs gasuli saukunis mecnieruli
kvlevebic, romlis Tanaxmad, kuWisa da Tormetgoja nawlavis wylulovan da
simsivnur daavadebebTan sisxlis 0(I) jgufi asocirdeba (Туманова & Томилина,
1969; Косяков, 1974), xolo A(II) fenotipi xSirad prevalirebs kuWisa da sarZeve
jirkvlis kibos, miokardis infarqtis dros (Прокоп с соавт., 1991; Мороков с
соавт., 2002). A(II) jgufis matarebeli individebi xSirad eqvemdebarebian
virusul respiratorul da gulis iSemiur daavadebebs. aseve, maTSi ufro
xSiria magistraluri gzebis aTerosklerozi, vidre 0(I) da B(III) jgufis
matareblebSi (Nazaretian et al., 1993; Кузнецов с соавт., 2000).
gulis iSemiuri daavadebis ganviTarebis maRali sixSire A(II) jgufis
matareblebSi dakavSirebulia antihemofiluri globulinis aqtiur
sinTezTan. iTvleba, rom es ukanaskneli aRniSnuli paTologiis
ganviTarebaSi udides rols TamaSobs da ganapirobebs Trombozis mimarT
36
organizmis midrekilebas (Шабалин с соавт., 1988). dafiqsirebuli iqna agreTve,
rom A(II) sisxlis jgufis mqone bavSvebi xasiaTdebian pnevmoniis mwvave
mimdinareobiT (Моисеев, 1987). aseve, virusuli hepatitiT xSirad avaddebian A
jgufis sisxlis matareblebi (Kiango et al., 1982). A(II) jgufis adamianebSi
sustad producirdeba interferonebi. swored, amiT SeiZleba aixsnas am jgufis
matareblebis sakmaod maRali midrekileba infeqciuri daavadebebis mimarT
(Донсков, 1987).
sahas (Saha, 1985) monacemebiT, asociaciuri kavSiri iqna napovni ABO
sistemas da keTrs Soris. kerZod, aRniSnuli seniT avaddebian A da O jgufis
mqone individebi. A jgufis matareblebi rezistentulebi aRmoCndnen ciebis
mimarT (Gupta & Chowdhuri, 1980). amerikelebSi O jgufis maRal prevalentobas
sifilisis mimarT aRniSnuli jgufis matarebel individTa maRali mdgradobiT
xsnian (Morrison, 1966).
arsebobs monacemebi, romlebic A(II) da B(III) jgufis maRal sixSires
adastureben TromboflebitiT daavadebul qalebSi. magram aRniSnuli
jgufebis matareblebi gacilebiT rezistentulebi aRmoCndnen qoleris
mimarT, vidre O(I) jgufis sisxlis mqone individebi. dadgenili iqna
magistraluri sisxlZarRvebis aTerosklerozis uaryofiTi asociacia 0(I)
fenotipis matarebel mamakacebSi. 0(I) jgufis matarebloba, SesaZloa, CaiT-
valos “damcvelobiT” faqtorad, radganac maTSi Semcirebulia zogierTi
saxis sisxlZarRvis paTologiis ganviTarebis riski (Кузнецов с соавт., 2000).
zogadad, adamianebis umravlesoba, romelTa eriTrocitebis zedapirze
ar gvxvdeba ABO sisitemis antigenebi, daavadebaTa mimarT mdgradobiT
gamoirCevian. amis dasturad, SesaZloa, gamoyenebuli iqnes O(I) jgufis
gavrcelebis maRali sixSire msoflios mosaxleobaSi.
pensilvaniis universitetis mecnierebis mier Catarebuli kvlevebis
Tanaxmad, genebi, romlebic pasuxismgebelia O(I) jgufis Camoyalibebaze,
organizms icaven gulis Setevisgan. amave dros, sxva kvlevebma aCvena O(I) jgufis
pacientebSi maRalia sisxldenis riski da sisxlis gadasxmis aucilebloba,
37
gulze qirurgiuli Carevis Semdeg. harvardis universitetis mkvlevarebi
askvnian, rom sisxlis aRniSnuli jgufis matareblebi midrekilni arian
gulis daavadebebisken (Hope, 2012).
korelaciuri kavSiri iqna dadgenili sisxlis jgufebsa da mwvave
dizenterias Soris. maqsimaluri koeficientebi B(III) da 0(I) jgufis mqone
pacientebSi dafiqsirda, xolo minimaluri _ A(II) jgufis matarebel
pirebSi (Земсков, 1994). skleroziT daavadebulTa 22,22% aRmoCnda B(III)
jgufis fenotipis matareblebi, maSin, roca sakontrolo jgufSi misi
gavrcelebis sixSire 11.10%-is tolia (Markovic et al., 1991).
ABO sistemis sisxlis 0(I), A(II) da B(III) jgufis matareblebSi arsebobs
gansxvavebuli imunuri pasuxi. kerZod, sinTezirebuli jgufspecifikuri,
bunebrivi antisxeulebi IgG da IgM klasis imunoglobulinebia. amasTan,
cnobilia, rom А(II) da В(III) jgufis matareblebi upiratesad asinTezeben IgM
klasis antisxeulebs, maSin, roca 0(I) jgufis matareblebSi IgM-sTan erTad
damatebiT sinTezdeba maRalaviduri IgG (anti-A an anti-B). isini aqtiurebi
arian 37оС-ze da floben gamoxatul hemolizur Tvisebas. am mizezis gamo
АВ0 sistemis mixedviT gansxvavebuli fenotipebis matareblebi bunebaSi
farTod gavrcelebuli А- da В- substanciebis eliminaciis araerTgvarovan
unars floben (Issitt, 1985; Dean, 2005). gamovlenili iqna asociacia ABO sistemas
da simsivniT, sifilisiT, diabetiT, ciroziT, gripiT, pnevmoniiT, bronqitiT
da asTmiT gamowveul sikvilianobas Soris (Masse et all, 1979).
sasunTqi sistemis daavadebebidan cnobilia, rom bronquli asTmiT da
mwvave pnevmoniiT daavadebul pirebSi O(I) jgufis maRali sixSire vlindeba
(Джавишеишвили и Ксенофонтов, 1981).
ABO sistemis antigenebis korelacia filtvis tuberkulozTan. sxvadasxva
populaciaSi tuberkulozsa da ABO sistemis antigenebs Soris asociaciuri
kavSirebis gamosavlenad Catarebul kvlevebSi alternatiuli daskvnebi
fiqsirdeba. rigi mecnierebisa adasturebs, rom ar arsebobs mniSvnelovani
asociacia aRniSnuli sistemis antigenebs da filtvis tuberkulozs Soris
38
(Saha, 1965; Saha & Banerjee, 1968; Reddy & Usha, 1990; Seth & Chahal, 2003; Ukaejiofo &
Nubila, 2006.), maSin, roca, sxvebi aRniSnul faqts uaryofen (Kothare, 1959; Shenoy &
Daftary, 1962; Navani & Narang, 1962; Nath et al., 1963; Sidhu et al., 1974; Mourant et al., 1976;
Ramachandraiah et al., 1984; Bhasin, 1994).
rigi mecnierebis monacemebiT, tuberkuloziT daavadebul pacientebSi
maqsimaluri sixSiriT dafiqsirda 0 (I) da Semdgom B (III) fenotipuri jgufebi,
xolo minimaluri sixSiriT A(II) jgufi (Rao, 1994; Platonova, 1999). tiagisa da misi
TanamSromlebis mier tuberkuloziT daavadebul mgb+ pacientebSi, B (III)
fenotipuri jgufi maqsimaluri sixSiriT gamovlinda, xolo Semdgom adgilze
0 (I) fenotipuri jgufi _ donorul populaciasTan SedarebiT (Tyagi et al., 2010).
naumovisa da TanamSromlebis (Naumov et al.,1993) mier dadgenilia, rom
filtvis tuberkuloziT daavadebulebSi sakontrolo donorul jgufTan
SedarebiT, 0(I) jgufi maRali sixSiriT vlindeba. A(II) jgufis mqone pirebSi
ki daavadeba dabali sixSiriTaa warmodgenili da maT yvelaze naklebad
aReniSnebodaT postoperaciuli garTulebebi.
viskumis (Viskum, 1975) kvlevis Sedegad tuberkuloziT daavadebul
pacientebSi dafiqsirda O da AB jgufis gamovlenis maRali sixSire. amave
avtoris mier SeniSnuli iqna O jgufis matarebel daavadebulTa
sikvdilianobis maRali ricxvi, maSin, roca am mxriv dabali maCvenebelia
SeniSnui A jgufis matareblebSi.
ABO sistemis antigenebis asociaciuri kavSirebi Seswavlili iqna
daavadebis formebSic. MmkvlevarTa mier dafiqsirebulia tuberkulozis
msubuqi forma da mkurnalobis Sedegianoba 0 (I) da A (II) jgufis matareb-
lebisaTvis, maSin, roca B (III) jgufis matareblebSi mkurnalobis kursi
xSirad uSedegoa (Volkova et al., 1991; Platonova, 1999).
tuberkulozTan sisxlis jgufuri antigenebis da alelebis asociaciur
kavSirs adasturebs singapuris Cinur populaciaSi (Saha, 1965), iaponelebSi
(Hirano, 1972), eskimosebSi (Overfield & Klauber, 1980) Catarebuli kvlevebi,
romlebmac gamoavlina tuberkulozis mniSvnelovani asociacia B antigenTan
39
da, Sesabamisad, B da AB fenotipur jgufebTan. B antigenTan asociaciuri
kavSirebi gamovlinda indoelebSi, sadac, aseve, tuberkuloziT daavade-
bulebSi mniSvnelovani sixSiriT A(II) fenotipic dafiqsirda (Jain, 1970; Saha,
1985; Seth & Chahal, 2003; Saha & Banerjee, 2003). aseve, unda aRiniSnos, rom raos da
TanamSromlebis (Rao et al., 2012) monacemebiT, indoeTis teritoriaze mcxovreb
andras regionis tuberkuloziT daavadebul populaciaSi dafiqsirda sisxlis
B(III) da AB(IV) fenotipuri jgufebi, xolo Tamarias (Thamaria, 2010)
monacemebiT, indურ populaciaSi dafiqsirebuli iqna alternatiuli, daava-
debis 0(I) jgufTan asociaciuri kavSiri.
eTnikur jgufebSi eriTrocitur antigenebTan gansxvavebuli asociaciuri
kavSirebis gamovlena, SesaZloa, dakavSirebuli iyos eTnikur jgufebSi maTi
ganawilebis sxvadasxva sixSiresa da daavadebis multifaqtorul bunebaze.
Rh-Hr sisxlis jgufebis gavrceleba da misi asocireba daavadebebTan.
rezus sistema adamianis erT-erTi yvelaze polimorfuli da kompleqsuri
imunogenetikuri sistemaaDda moicavs 49 damoukidebel antigens. antigenebis
polimorfuloba serologiurad sisxlis mraval fenotipur jgufs iZleva.
klinikuri TvalsazrisiT yvelaze mniSvnelovania D, C, E, c, e antigenebi (Avent
& Reid., 2000).
Rh faqtori ganpirobebulia ori, erTmaneTTan Wdomili RHD da RHCE
genebiT, romlebic moTavsebulia 1 p36.1 – p34-3-Si. RHD lokusiT kontroldeba
D antigenis produqcia, RHCE lokusi ki ganapirobebs C an c da E an e
antigenebis sinTezs (Оловникова, 2001).
Rh sistemis antigenebi maRali imunogenuri TvisebebiT xasiaTdebian.
gansakuTrebuli imunogenuri aqtivobiT D antigeni gamoirCeva, romelic 30-ze
met epitops Seicavs da xSirad iwvevs alosensibilizacias D uaryofiT
pirebSi (Avent & Reid, 2000).
RHCE da RHD genebiT kodirebuli haplotipebidan (genuri kompleqsi)
yvelaze maRali sixSiriT 8 haplotipia warmodgenili: CDE (Rz), Cde (R1), cDE
(R2), cDe (Ro), cde (r), Cde (R’), cdE (R’’), CdE (Ry). gamoyofilia aRniSnuli sistemis
40
18 fenotipuri jgufi: CDE, CDEe, Cde, CcDE, CcDEe, CcDe, cDE, cDEe, cDe, CD(-)E,
CD(-)Ee, CD(-)e, CcD(-)E, CcD(-)Ee, CcD(-)e, cD(-)E, cD(-)Ee, cD(-)e. zemoT CamoTvlilTagan
Cde, cDE, cDe da cde sxvebTan SedarebiT ufro farTo gavrcelebiT xasiaTdeba.
maTi sixSire damokidebulia krosingoveris albaTobaზე (Syst. immunogen.
Polymorp., 2000).
msoflios mosaxleoba xasiaTdeba Rh-polimorfizmiT. D da d alelebis
sixSiriT evropeiduli da negroiduli rasebi mniSvnelovnad gansxvavdebian
mongoloidurisagan. mongoloiduri populaciisaTvis d aleli iSviaTobas
warmoadgens, zogierT maTganSi ki saerTod ar gvxvdeba, maSin, roca
aRmosavleT evropaSi misi sixSire 15-20%-ia, dasavleT evropaSi (magaliTad,
baskebSi) ki _ 40-50%-s aRwevs.
adgilobriv amerikelebSi, vidre maT msoflios sxva regionebis
mosaxleoba Seereoda, d alelis koncentracia praqtikulad ar fiqsirde-
boda, xolo D alelis koncentracia 99-100%-s Seadgenda, Sua saharis
afrikelebSi 97-99% Rh+-ia, xolo aRmosavleT aziaSi - 93-99%.
msoflios mosaxleobaSi rezusis sxva antigenebis gavrcelebis sixSire
Semdegnairia: C - 70%; E - 30%; e - 97% (Умнова c соавт., 1979).
rac Seexeba Rh-haplotipebis gavrcelebas CDe(R1), igi yvelaze farTod
gavrcelebuli haplotipia evropaSi, SedarebiT naklebad -afrikaSi (0,05-0,09).
cDE(R2) haplotipi mniSvnelovnad farTodaa dafiqsirebuli indielebSi
(0,50). cDe (R0) koncentracia msoflios sxva regionebTan SedarebiT maRalia
(0.90) afrikis kontinentze. Cde haplotipis maqsimaluri sixSire evropaSi
fiqsirdeba da sruliad ar gvxvdeba Soreul aRmosavleTSi. msoflios
yvela populaciisTvis iSviaTi CDE-haplotipi SedarebiT maRali koncentra-
ciiT gvxvdeba indur da avstraliur tomebSi, xolo aseve iSviaTi cdE haplotipi
SedarebiT xSirad - iaponur tomebSi.
Rh sistemis kvlevis TvalsazrisiT, saqarTveloSi monacemebi sakmaod
mwiria. cnobilia, rom dasavleT saqarTveloSi D(+) fenotipi gvxvdeba 95,9%-
is, xolo D(-)ki _ 4,1%-is sixSiriT. aRniSnul populaciur jgufSi D
41
alelis sixSire 0,796-is tolia, d alelisa ki _ 0,204 (Джавишеишвили и
Ксенофонтов, 1981). ukanaskneli monacemebiT, safuZvlianad iqna Seswavlili Rh
sistemis antigenebisa da haplotipebis gavrceleba aWaris regionSi, sadac D -
78,2%; e- 97.6%; c – 90.2%; C – 53.4%; E-21, 12% sixSiriT gvxvdeba. Sesabamisad,
aRniSnuli sistemis alelebi Semdegi sixSiriT aris warmodgenili: D – 0.54; d –
0.43; C-0.28; c-0.74; E- 0.11 da e – 0.87. aWaris regionisTvis farTo gavrcelebiT
dafiqsirda cde – 0.436 da Cde – 0,192 haplotipebi (Nagervadze, 2010).
daavadebebTan rezus sistemis asociaciis Sesaxeb zogierTi avtoris mier
naCvenebi iqna Rh(D) antigenis korelacia alcheimeriT daavadebul pacientebSi,
sadac pacientTa 95,55% rezus dadebiTi, 84,29% rezus uaryofiTi faqtoris
matarebeli aRmoCnda (Markovic et al., 1991). aseve, rezus dadebiTi, CcDe fenotipis
kavSiri gamovlenili iqna kuWis wylulTan (Пелешук c соавт., 1974). rezus
uaryofiT pacientebSi mcirea aortis anevrizmiT daavadebis albaToba. rezus-
uaryofiT adamianebSi gacilebiT ukeT funqcionirebs humoruli imuniteti,
xolo rezus-dadebiT pirebSi ki -ujreduli imuniteti (Norrgard et al., 1984
Донсков, 1987, 2001).
baqteriuli anatoqsinebiT gamowveuli imunuri pasuxis intensivoba
maRalia D da Е antigenebis matarebl pirebSi (Вереш с соавт., 1985). gulis
iSemiuri daavadeba maRali sixSiriT SeiniSneba CC genotipis mqone individebSi,
vidre Cc genotipis matareblebSi (Nazaretian et al., 1993).
tuberkulozTan rezus faqtorisa da misi antigenebis korelaciuri
kavSiris Sesaxeb Zalian mwiri masalebi moipoveba. mecnierTa nawili
tuberkulozTan Rh faqtoris pirdapir korelacias uaryofs. magaliTad, raos
(Rao et al., 2012) mier Catarebuli kvlevebis mixedviT A(II) sisxlis jgufis mqone
pacientebSi Rh+ faqtoris mniSvnelovnad maRali sixSire dafiqsirda sxva
kombinaciebTan SedarebiT. arsebobs monacemebi, rom ufro meti rezus-
uaryofiTi pacienti daiRupa tuberkuloziT, vidre rezus-dadebiTi (Viskum,
1975).
42
Kell sistemis sisxlis jgufebis gavrceleba da misi asocireba
daavadebebTan. Кеll sistemis genuri lokusi moTavsebulia meSvide
autosomur qromosomaSi _ 7q 32 – q 36. sistema kompleqsuria da moicavs 25
antigens (K, k; Kpa, Kpb; Jsa, Jsb…). yvelaze maRali imunogenurobiT К antigeni
gamoirCeva, romlis imunuri aqtivoba mcirediT Tu Camouvardeba rezus D
antigenis aqtivobas (Dean, 2005).
К antigenis gavrcelebis sixSire msoflio mosaxleobaSi sakmaod dabalia
(10%). homozigotur mdgomareobaSi ki igi mxolod 0.3%-ia (Рагимов и Дашкова,
2004). evropeidebs Soris Kell (K)-s Sexvedris albaToba 3-dan 12%-mdea.
evropeodebSi misi gavrcelebis sixSire 9%-ia (Dean, 2005), arabeTis mosax-
leobaSi -10%. espaneTis erT-erT lokalur populaciaSi maqsimaluri
sixSire - 31,71% dafiqsirda. negroidebSi da mongoloidebSi K antigeni
iSviaTad gvxvdeba, xolo Cinelebsa da iaponelebSi igi praqtikulad ar
aris gamovlenili (Mourant et al., 1978; Bowman et al., 1992). saqarTveloSi Kell
sistemis antigenebis gavrcelebis Sesaxeb informacia moipoveba mxolod aWaris
regionis masStabiT. К+ fenotipi aq 6%-ia, p(K) alelis koncentracia 0.04-is
tolia (Nagervadze, 2010).
paTologiebTan Кеll sistemis antigenebis kavSiri praqtikulad
Seuswavlelia. literaturuli wyaroebidan cnobilia Kell-dadebiTi sisxlis
jgufis maRali sixSire aortis anevrizmiT daavadebulebSi (Norrgard et al.,
1984). tuberkulozTan Kell sistemis antigenebis asociaciis Sesaxeb informacia
literaturul wyaroebSi TiTqmis ar moipoveba.
MN sisxlis jgufebis gavrceleba da misi asocireba daavadebebTan. MN-Ss
sistemis antigenebi kodirebulia GYPA da GYPB genebiT, romlebic
moTavsebulia me-4 qromosomaSi (4q28-q28) (McKusick, 1985; Dean, 2005). MN sistemis
43 antigenidan yvelaze mniSvnelovania M, N, S, antigenebi. maTgan SedarebiT
ukeT M da N antigenebia Seswavlili (Dean, 2005; Reid, 2009).
43
literaturuli monacemebiT, evropeodebSi M antigenis sixSire 78%-ia; N-
72%; S-55% xolo s-89% (Dean, 2005). murantis monacemebiT, saqarTveloSi,
kerZod, qalaq Tbilisis mcxovreblebSi M fenotipis gavrcelebis sixSire
Seadgens 39,6%-s, MN –is - 46,0; N fenotipisa ki _ 0,374%-s (Mourant et al., 1979).
nagervaZis monacemebiT, aWaris regionSi M fenotipi 50,2%; N - 29.8%; xolo MN
20,2% sixSiriT aris warmodgenili (Nagervadze, 2010).
rac Seexeba daavadebebTan MN sistemis korelacias, MN fenotipuri
jgufis maRali sixSire aRiniSneba Saqriani diabetiT daavadebulebSi
(Ксенофонтов, 1974). aseve, mwvave pnevmoniiT xSirad avaddebian MN fenotipis
matarebeli bavSvebi (Алтухов c соавт., 1981). aRniSnulia M fenotipis maRali
sixSire aTeroskleroziT daavadebulebSi, xolo N fenotipuri jgufi
sakontrolo jgufTan SedarebiT ufro xSirad gvxvdeba osteoqondroziT
daavadebul pirebSi (Колодченко., 1979).
cnobilia, rom MN sistemis makodirebel GYPB genSi (asinTezirebs
jgufobriobis ganmsazRvrel A da B glikofurinebs) momxdari konversia
gavlenas axdens malariisadmi mgrZnobelobaze (Ko., 2011).
MN-Ss sistemasa da gul-sisxlZarRvovan daavadebebs Soris garkveuli
asociaciuri kavSiri iqna napovni (Gleiberman et al., 1984). SeniSnulia agreTve M
jgufis matarebeli pirebis gansakuTrebuli midrekileba alkoholis mimarT
(Kojic et al., 1977). botinisa da misi TanamSromlebis mier dadgenili iqna MN
sistemis antigenebis dadebiTi korelaciuri kavSiri asTmasTan. kerZod,
donorebTan SedarebiT M fenotipis maRali sixSire - araalergiul asTmasTan,
xolo N antigenisa - alergiul asTmasTan. arsebobs varaudi, rom SesaZloa, MN
sistemis genetikuri variabeloba gavlenas axdendes baqteriul da virusul
konkurenciaze, sasunTqi sistemis lorwovani garsis dazianebis SemTxvevaSi
IgE-s hiperproduqciis ararsebobisas, rac gavlenas axdens asTmur reaqciebze
(Bottini et al., 2005).
informacia MN sistemisa da filtvis tuberkulozis korelaciuri
kavSirebis Sesaxeb literaturul wyaroebSi ver iqna moZiebuli.
44
I.6. organizmis imunuri dacvis meqanizmebi
mikobaqteriis mimarT ganviTarebul imunur pasuxSi
tuberkulozis ganviTarebaSi fundamentur rols asrulebs M.
Tuberculosis-is mimarT organizmis imunuri pasuxi, rasac daavadebulebTan
SedarebiT inficirebulTa gacilebiT maRali ricxvi adasturebs. infeqciuri
agentis bedi organizmSi moxvedris Semdeg, organizmis sxva faqtorebTan
erTad, damokidebulia mis mimarT ganviTarebul araspecifikur Tu specifikur
imunur pasuxze. arasaTanado SemTxvevaSi inficirebul individSi daavadeba
klinikuri saxiT vlindeba. imunuri sistemis arsebiTi rolis damadasturebel
faqts warmoadgens isic, rom mniSvnelovnad izrdeba tuberkuloziT avadoba
adamianis imunodeficitis virusiT koinfeqciisas (Palomino et al., 2007).
aseve, kargad aris cnobili, rom BCG vaqcinaciac saTanadod ver
uzrunvelyofs tuberkulozis prevencias. aRniSnuli faqtebidan gamomdinare,
Seiqmna aSkara moTxovnileba axali antituberkulozuri Tu sxva saxis
qimioTerapiuli preparatebis da axali, maRalefeqturi vaqcinis Sesaqmnelad
(Palomino et al., 2007).
adreuli kvlevebis umravlesoba, ZiriTadad, xazs usvamda mikrobis
virulentobas da maspinZeli organizmis imunuri sistemisagan Tavdacvis
strategiebs. naklebi yuradReba eqceoda TviT makroorganizmis damcvelobiTi
sistemis arsebiT rols am procesSi (Shinnic et al, 1995; Soolingen, 2001; Smith, 2003).
bolo periodis kvlevebSi xazgasmulia, rom daavadebis klinikuri ganviTareba
Tanabrad ganisazRvreba, rogorc mikobaqteriis virulentobiT, ise maspinZeli
organizmis damcvelobiTi meqanizmebiT (Rajpal et al., 2011). kvlevebi mimdinareobs,
rogorc mikobaqteriis biologiuri Taviseburebebis gasarkvevad, ise adamianis
mier daavadebis winaaRmdeg ganviTarebuli imunuri pasuxis meqanizmebis
Sesaswavlad (Schluger, 2001; Casanova& Abel, 2002). mikobaqteriuli infeqciis
45
Sedegi ganisazRvreba imunuri sistemis, maspinZeli organizmis da mikobaqteriis
gadarCenis strategiebis erTobliobiT.
antituberkulozur dacvaSi TanabarmniSvnelovnadaa CarTuli, rogorc
Tandayolili, ise SeZenili imuniteti, romlebic komplementurad da
sinergiulad moqmedeben. am procesSi CarTuli imunuri meqanizmebis srul-
yofilad gageba samomavlod migviyvans, rogorc prevenciis, aseve Terapiis
axali midgomebis mignebamde (Flyn & Chan., 2001; Kaufmann., 2001; Raja., 2004).
Tandayolili imunuri pasuxi M. Tuberkulosois-is winaaRmdeg.
tuberkulozuri infeqciis adreul stadiaze Tandayolili imuniteti
asrulebs mniSvnelovan rols, magram igi, aseve, SeZenili imunitetis
iniciaciisa da moqmedebis gasaRebia (Crevel et al, 2002).
M. Tuberkulosois-iT inficirebis SemTxvevaSi pirveli xazis damcveli
ujredebi, romlebic inhalirebul paTogenze moqmedebs, alveoluri
makrofagebia, romlebic STanTqaven da moineleben bacilas. gadamuSavebuli
bacila Semdeg etapze waredgineba T ujredebs, rac iwvevs mikobaqteriis mimarT
ujreduli imunitetis stimulirebas. makrofagebis mier baqteriis gamocnobas
da Semdeg mis STanTqmas ganapirobebs mis zedapirze arsebuli zedapiruli
receptorebi –komplementis receptori (CR- C3), manozas receptori,
skavenjeruli receptori, Fc-γ, CD14 fagocituri ujredebi (Schlesinger et al, 1993;
Pugin et al, 1994 Schluger & Rom., 1998; Le Cabec et al, 2000; Kaufmann, 2001).
mikobaqteriis raodenobis Semcirebisa da misi gavrcelebisagan Tav-
dacvis mizniT makrofagebi ganicdian apoptozs, rac TavisTavad anadgurebs
ujredSida bacilebs. am procesis mTavari mastimulirebeli faqtori aris
simsivnis nekrozis faqtori (TNFα) (Balcewicz-Sablinska et al, 1998). TNFα-
transmembranuli cilaa, romelic Tandayolil imunitetSi gamoicnobs
paTogenTan asocirebul molekulebs (PAMP), romlebic Tandayolili imunite-
tis saukeTeso samizneebs warmoadgenen (Medzhitov et al., 2001; Akira et al., 2001).
46
Toll cilebi citokinebis, qemokinebis, histoSeTavsebulobis mTavari
komleqsis cilebis, azotis oqsidis sinTetazas da sxvaTa sinTezs aaqtiveben.
ufro metic, TLR akontrolebs SeZenil imunitetsac (Iwasaki & Medzhitov., 2004).
kerZod, maT mier ligandebis gamocnoba iwvevs interleikin-12-is sinTezs,
romelic ganapirobebs Th0-is Th1 helperebad diferencirebas. TLR-ebi
astimulireben antigen-warmdgeni dendrituli ujredebis momwifebas (Medzhitov,
2001; Akira et al, 2001).
cnobilia, rom tuberkulozis mimarT imunur pasuxSi mTavari roli
alveolur makrofagebs akisriaT.Mmagram aRsaniSnavia, rom mikobaqteriiT
inficirebidan ramdenime dRis Semdgeg infeqciis kerebSi Cndeba neitrofilebi
(Pedrosa et al., 2000; Fultonet al., 2002). isini xels uSlian bacilis gamravlebas.
aseve fiqroben, rom isini akontroleben infeqcias qemokinebis produqciiT,
granulomebis CamoyalibebiT da a.S. (Riedel et at., 1997; Urban et al., 2006).
tuberkulozur kerebSi napovnia dendrituli ujredebis didi
raodenoba. isini Seicnoben, iWeren, gadaamuSaveben antigens da waradgenen
histoSeTavsebulobis mTavari kompleqsis (MHC) molekulebTan erTad.
(Banchereau 1998, Gumperz 2001).
filtvebSi mikobaqteriuli infeqciidan 21 dRis Semdeg bunebrivi
qilerebis raodenoba matulobs. isini umniSvnelod zrdian citotoqsi-
kurobas CD8+T-ujredebis mier IFNγ produqciis optimizaciis gziT. amiT,
garkveulwilad, xels uwyoben mikobaqteriiT inficirebuli ujredebis daSlas
(Vankayalapati et al., 2004).
adapturi imunuri pasuxi M. Tuberkulosois-is winaaRmdeg. araspecifikuri
imunuri pasuxi gavlenas axdens specifikuri imunuri meqanizmebis moqmedebaze,
romelic axorcielebs efeqtorul funqciebs. orive meqanizmi urTierTdamo-
kidebulia.
specifikuri ujreduli da humoruli imunitetis Seswavla tuberkulo-
ziT daavadebulebSi, jer kidev, koxis dros daiwyo. T-limfocitebi da
gaaqtivebuli makrofaguli sistema aregulirebs tuberkulozis infeqciisadmi
47
organizmis mdgradobas. antituberkulinuri antisxeulebis roli jer kidev ar
aris srulyofilad garkveuli.
ujreduli imunuri pasuxi. mas Semdeg, rac tuberkulozis Cxiri
makrofagSi SeiWreba, misi antigeni CD4+T-limfocitebs waredgineba MHCII
klasis molekulebTan erTad. isini mniSvnelovan rols asruleben M.tuberculisis
winaaRmdeg damcvelobiTi pasuxis ganviTarebaSi. maT gareSe SeuZlebelia
organizmSi bacilis zrdis kontrolireba. aRniSnuli SemTxvevebi xdeba
imunodeficitebisas (Caruso et al., 1999). CD4+T-ujredebi TavianT funqcias
citokinebis produqciiT axorcieleben. isini aaqtiveben makrofagebs da xels
uwyoben bacilis destruqcias (Serbina et al., 2001). aseve, SesaZloa, isini
monawileobdnen inficirebuli makrofagebis apoptozSi da sabolood _
baqteriis sicocxlisunarianobis reduqciaSi CD95 ligandis meSveobiT (Oddo et
al., 1998). Sesabamisad, tuberkulozuri infeqciisas organizmSi izrdeba T-
ujredebis done, romlis Semcireba daavadebis gamwvavebas iwvevs.
gansakuTrebuli funqcia aqvs γδ T-ujredebs. isini monawileoben lizisur
procesebSi, asinTezeben citokinebs (IL17 da IFN-γ) da monawileoben
citotoqsikur aqtivobebSi.
humoruli imunuri pasuxi. imis gamo, rom mikobaqteria ujredSida
paTogenia, xSirad miiCneven, rom humoruli imunuri pasuxi am SemTxvevaSi
damcvelobiT rols ver asrulebs. Tumca, sawyisi infeqciis mimdinareobisas
antisxeulebi, rogorc damoukideblad, ise citokinebTan kavSirSi, SesaZloa,
uzrunvelyofdnen lorwovan garsebSi baqteriis SeWris prevencias. arsebobs
monacemebi, rom humoruli imunuri pasuxi mniSvnelovan rols asrulebs iseTi
infeqciebis mimarT, rogoricaa: qlamidiuri respiratoruli (Skeldin, 2006),
aqtinomicetebiT da, maT Soris, M. Tuberculosis-iT gamowveuli infeqciebis
(Salinas-Carmona et al., 2004, Williams et al., 2004, Reljic et al., 2006) dros.
M. tuberculosis-gan dacvis humoruli imunuri pasuxi srulyofilad ar aris
Seswavlili. mikobaqteriuli infeqciisas antisxeulebis damcvelobiTi
48
funqciis garda, specifikuri antituberkulozuri antisxeulebi, SesaZloa,
mniSvnelovnad Rirebuli iyos klinikur-serologiuri diagnozirebisas.
serologiuri meTodebi Tavisi simartiviT, xelmisawvdomobiT da dabali
fasiT mimzidveli sadiagnostiko saSualeba iyo me-20 saukuneSi. jer kidev 1898
wels arlongma aCvena, rom pacientebis sisxlis Srati awebebda tuberkulozis
bacilebs. me-20 saukunis 70-ian wlebSi mecnierebi Seecadnen, imunofermen-
tuli analizis meTodebis gamoyenebiT gamoevlinaT serodiagnostirebis-
Tvis optimaluri antigeni. im droisaTvis aqcenti keTdeboda kompleqsur
antigenebze, rogoricaa: mTliani baqteria, kulturis filtrati, baqteriuli
eqstraqtebi - tuberkulini da maTi sufTa narCenebi (PPD). SemdgomSi, analizi
tardeboda gasufTavebul antigenebze, romlebic moicavda cilebs, lipopoli-
saqaridebs da glikolipidebs (Ag85, 38-kDa cila, LAM an diaciltrehalozebi).
daavadebul da janmrTel populaciebSi 38-kDa, rMTB48, rCFP-10/ESAT-6–s da
HLA-s SeswavliT maT mimarT gamomuSavebuli antisxeulebis gacilebiT
maRali koncentraciebi gamovlinda tuberkuloziT daavadebul pacientebSi,
janmrTelebTan SedarebiT (Bothamley, 1995; Lyashchenko et al, 1998; Xueqiong et al,
2010). Tumca, aRsaniSnavia, rom maRali specifikuroba zusti diagnostikuri
TvalsazrisiT verc erTma maTganma ver aCvena (Singh et al., 2003; Raqib et al., 2003;
Lopez-Marin et al., 2003; Julián at al., 2004).
SratSi mocirkulire antisxeulebi (IgG, IgA, IgM) zrdian imunitetis
dones sxvadasxva meqanizmis (toqsinebis neitralizacia, ofsonizacia,
komplementis aqtivacia, citokinebis sekreciis stimulacia, antisxeul-
damokidebuli citotoqsikuroba, antigen-warmdgenis reaqciebis gazrda)
saSualebiT. mTeli rigi kvlevebi miuTiTebs, rom anti-mikrobuli antisxeulebi
mniSvnelovan rols asrulebs antituberkulozuri imunuri pasuxis
sxvadasxva etapze (Costello et al., 1992; Teitelbaum 1998; Hoft et al., 2002; Williams et al.,
2004). valieris mier naCvenebi iqna, rom specifikuri antisxeulebi zrdian BCG-s
internalizacias da ganadgurebas makrofagebisa da neitrofilebis mier.
49
ufro metic, antisxeulebiT SefuTul BCG bacilebs imunur pasuxSi
dendrituli ujredebi ukeT gadaamuSaveben da warudgenen CD4+ da CD8+ T-
ujredebs (De Valliére,2005).
antisxeulebis mier mikrobTa internalizacia da maTi pirdapiri
ganadgureba specifikuri mikrobuli samizneebis gamocnobis xarjze cnobili
ar aris. magram, eqsperimentSi BCG vaqcinaciiT gamowveuli humoruli imunuri
pasuxis Seswavlisas ikvlevdnen 17 saxis rekombinantul, mikobaqteriul
cilovan antigens (bunebriv Ag85 kompleqss, LAM da mikobaqteriis gamonawurs).
aRmoCnda, rom LAM-reaqtiuli Sratis mimarT imunur pasuxSi IgG-is done
mniSvnelovnad iyo gazrdili, rogorc vaqcinirebul individebSi, aseve
tuberkulozur pacientebSi. oraluri BCG vaqcinaciisas ki LAM-reaqtiuli
sekretoruli IgA donis mniSvnelovani zrda gamoikveTa (Brown et al., 2003).
aRniSnuli faqti miuTiTebs, rom Sratis imunoglobulinebi aqtiuradaa
CarTuli organizmis antimikobaqteriul dacvaSi da maTi donis gamovlena M.
Tuberculosis-iT inficirebis indikators warmoadgens.
IgA-s antimikobaqteriuli moqmedebis gasarkvevad Tagvebze Catarebul
eqsperimentSi gamovlinda, rom monoklonuri IgA-s intranazaluri (aerozoli)
inokulireba alfa kristalinis (stresuli faqtori) winaaRmdeg, daaxloebiT
9 dReSi 10-jer amcirebs mikobaqteriis kolonia-warmomqmnel erTeuls (CFU)
filtvebSi. rogorc monomeruli, ise polimeruli IgA-s Seyvanam Tanabrad
Seamcira kolonia-warmomqmneli erTeulebi, rac SesaZloa, gamowveuli iyos
imiT, rom inficirebuli filtvis makrofagebSi antisxeulebis samizneebs
warmoadgends Fcα receptorebi (Fc-αR) da ara polimeruli imunoglobu-
linuri receptori (poli-IgR). rogorc mosalodneli iyo, dacva ganxor-
cielda xanmokle periodis manZilze, rac SesaZloa, aixsnas imunoglobulinis
intranazaluri Seyvanis Semdeg misi swrafi degradaciiT (Williams et al., 2004;
Palomino et al., 2007).
50
mogvianebiT, tuberkuloziT daavadebul cxovelebSi jer gama
interferonebis inokulirebas axdendnen, xolo sami dRis Semdeg SehyavdaT
IgA-s drois gansxvavebuli intervaliT (2sT, 2 da 7 dRe). Sedegad CFU 10-is
nacvlad Semcirda 17-jer, iseve, rogorc, Semcirda granulomatozuri
infiltracia filtvSi (Reljic et al., 2006). amrigad, INF-γ da IgA, tuberkulozur
imunodeficitur pacientebSi SesaZlebelia gamoyenebuli iqnas, rogorc
profilaqtikuri an damatebiTi qimioTerapiuli samkurnalo saSualeba.
garda IgA-isa, IgG-c mniSvnelovan rols asrulebs tuberkulozuri
infeqciis marTvis procesSi. qvemo respiratoruli traqtis lorwovan garsebSi
IgA-Tan erTad aRmoCenili iqna IgG (Boyton & Openshaw., 2002).
jainisa da misi TanamSromlebis (Jain et al., 1984) mier filtvis
tuberkuloziT daavadebulebSi imunoglobulinebis donis Seswavlisas,
aseve gamovlenili iqna IgG-sa da IgA-s mniSvnelovnad maRali done donorebTan
SedarebiT. IgA mniSvnelovnad maRali sixSiriT qalebSi dafiqsirda, xolo IgG-
sa da IgM-s done sqesis mixedviT ar varirebda. daavadebis klinikuri
formebis SemTxvevaSi IgG-s maRali done gamovlenili iqna tuberkulozis
fibro-kavernozul formaSi. zogierTi avtoris mier dafiqsirebuli iqna, rom
IgM klasis imunoglobulinis mateba SeiniSneba daavadebis adreul stadiaze,
xolo daavadebis Semdeg stadiebze gazrdili IgG-is koncentracia, SesaZloa,
kavSirSi iyos baqteriebis aqtiuri ganadgurebis procesTan (Ferdous et al., 2008).
specifikuri da araspecifikuri imunuri markerebis garda, romelic
moicavs M. tuberculosis Sratis specifikur antisxeulebs, humorul imunur
pasuxSi CarTulia sxva iseTi nivTierebebic, romelTa arseboba organizmSi
daavadebis indikatorad SeiZleba miviCnioT, rogorc filtvis, ise filtvgare
tuberkulozis SemTxvevaSi. aRniSnul indikatorebs ekuTvnis T-limfocitebis
fermentuli adenozin-deaminazebi, makrofagebis aqtivaciis neopterinuli
produqtebi, mononukleuri ujredebis zedapiruli cila β2 mikroglobulini,
T- ujredebis xsnadi interleikin (IL)-2-is receptorebi, iseve, rogorc xsnadi
51
CD4 da CD8 receptorebi, makrofagebisa da T-ujredebis adheziis molekulebi
da mwvave fazis reaqtiuli cilebi (Hosp et al., 1997; Baumer et al., 1998).
antimikobaqteriul dacvaSi, aseve, CarTulia sxvadasxva saxis
mediatorebi: pre-inflamatoruli citokinebi - IFN-γ (Lalvani et al., 1998), romlis
producirebas da CD4 T- ujredebis diferencirebis stimulirebas IL-12 –
iwvevs (Cooper et al., 1997; Flynn & Chan, 2001). cnobilia, rom IFN-γ-s, IL-12-sa da
misi receptorebis makodirebel genebSi napovni mutaciebi asocirdeba mZime
mikobaqteriul infeqciasTan (Malik & Schurr, 2002). aseve, IL-1β citokini
aqtiuradaa CarTuli granulomebis formirebaSi tuberkulozuri infeqciisas
(van Crevel et al., 2002). xolo IL-18 astimulirebs sxva preinflamatoruli
citokinebis, qemokinebis da transkripciuli faqtorebis produqcias (Netea et al.,
2000). IL-18-iT blokirebul TagvebSi maRali mgrZnobeloba gamovlinda BCG-iT
da mikobaqteriiT inficirebisas (Sugavara et al., 2002).
anti-inflamatoruli citokinebidan aRsaniSnavia IL-10. igi sinTezirdeba
makrofagebis mier mikobaqteriis STanTqmis Semdeg, aseve sinTezirdeba T-
ujredebis mier (Shaw et al., 1998; Boussiotis et al., 2000). igi Trgunavs IFNγ-s, Il-12-s
da TNFα-s producirebas (Fulton et al.,1998). TagvebSi misi blokirebis
SemTxvevaSi mikobaqteriisadmi mdgradoba aRar vlindeboda (North et al., 1999),
Tumca, misi roli bolomde garkveuli ar aris.
TGFβ sinTezirdeba monocitebisa da dendrituli ujredebis mier, mas
Semdeg, rac mikobaqteriiT stimulireba moxdeba (Toossi et al., 1995). is Trgunavs
T-ujredebis proliferacias, IFNγ-s produqcias, makrofagebis mier antigenis
wardgenis reaqciebs, pro-inflamatoruli citokinebis produqcias da
ujredul aqtivacias. cnobilia, rom isini tuberkulozisas iwveven qsovilebis
dazianebas da fibrozs (Toossi & Ellner, 1998).
TagvebSi tuberkulozis gamwvavebisas aRiniSna IL-4 -is donis mateba
(Howard & Zwilling, 1998). cnobilia, rom ujreduli imuniteti IL-4 -is produqciis
52
Semdeg ar stimulirdeba (North et al., 1999), amitom misi roli klinikuri Sedegis
TvalsazrisiT mniSvnelovania.
tuberkulozis mimdinareobisas mniSvnelovania qemokinebi - IL-8,
monocitis qemoatraqtuli cila-1 (MCP-1) da RANTES (Zhang et al., 1995; Kurashima
et al., 1997; Sadek et al.,1998; Pedrosa et al., 2000). cnobilia, rom tuberkulozis
mkurnalobis Semdeg pacientebis SratSi IL-8 done aweulia (Murphy, 1997). MCP-1
sinTezirdeba makrofagebisa da monocitebis saSualebiT da misi done
tuberkulozur pacientebSi maRalia (Kurashima et al., 1997). RANTES - qemokini
tuberkulozur procesebSi pasuxismgebelia granulomebis warmoqmnaze
(Chensue et al.,1999).
filtvis tuberkulozis aqtivaciisas SratSi gazrdilia komplementis
cilebis C3 –sa da C4-s koncentraciebi (Bothamley, 1995). aseve, isini ganixileba,
rogorc daavadebis aqtivaciis markerebi (Bekker et al., 1998; Juffermans et al., 1998;
Verbon et al., 1999).
tuberkulozis dros ujreduli da humoruli imunuri pasuxis
meqanizmebis srulyofilad codna, SesaZloa, gamoyenebul iqnes
tuberkulozis axali srulyofili vaqcinis Sesaqmnelad, alternatiuli
imunoTerapiis, daavadebis garTulebis prevenciisa da misi marTvis saqmeSi.
53
I.7. tuberkulozi da M. tuberculosis-is mimarT
organizmis mgrZnobelobaSi monawile genebi
tuberkulozis gamomwvevi baqteriiT inficirebisas daavadebis klinikur
ganviTarebaze mepatrone organizmis genetikuri faqtorebis mniSvneloba eWvs
aRar iwvevs (Bellamyet al.,1998; Bellamy, 2005; Freidin et al., 2006; Hill, 2006; Ottenhoff, 2005;
Remus, 2003). ukanaskneli ori aTwleulis manZilze ganxorcielebuli
kvlevebiT dadasturebulia, rom tuberkulozis mimarT arsebobs organizmis
genetikuri winaswarganpirobebuloba (Stead et al.,1990; Shaw et al.,1997; Li et al.,
2006/2006; van der Eijk et al.,2007). Catarebuli kvlevebi ZiriTadad tuberkulozis
filtvis formas exeba, radgan tuberkulozuri daavadebebis 95% masze mo-
dis da filtvgareSe formebTan SedarebiT srulyofiladaa Seswavlili.
identificirebuli iqna filtvis tuberkulozis mimarT mgrZnobelobis
ara erTi geni da genTa aleli, romelTa, Tundac erTnukleotidiani cvlileba
ganapirobebs misi funqciis Secvlas da gavlenas axdens daavadebis mimarT
organizmis sensibilobasa Tu mdgradobaze. magram amavdroulad,
tuberkulozis mimarT mgrZnobiare kandidati genebis Sesaxeb miRebuli
monacemebis mixedviT zogadi daskvnebis gakeTebas arTulebs is garemoeba, rom
kvlevebi gansxvavebul populaciebSi gansxvavebul, zogjer sapirispiro
Sedegebs iZleva. Tu erTi romelime konkretuli geni an genis aleli asocirebu-
lia tuberkulozTan konkretul populaciaSi, aRniSnuli asociacia ar
fiqsirdeba sxva populaciaSi (Li et al., 2006). amis mizezi xSirad konkretuli
populaciisTvis damaxasiaTebeli balansuri polimorfizmis Sedegia, romelic
konkretul garemoSi evoluciurad TviT am populaciebTan erTad Camoyalibda.
gansxvavebuli alelebis Semcveloba populaciur doneze pirdapir
gansazRvravs tuberkulozis mimarT populaciis mgrZnobelobas an mdgradobas.
xSirad populaciebSi alelur da araalelur genebTan urTierTqmedebis
balansi gansazRvravs specialuri imunuri genebis eqspresirebis dones da
xasiaTsac, Sesabamisad Sedegebic gansxvavebulia.
54
tuberkulozTan asocirebuli genebis TiTqmis 90% organizmis imunuri
sistemis makontrolebeli genebia, romlebic infeqciuri agentebis mimarT
damcvelobiT imunur pasuxs aviTareben. mecnieruli kvlevebis mTavari
fokusic, swored, maTi genetikuri lokusebis Seswavlisa da daavadebasTan
asociaciis gamovlenis mimarTulebiT warimarTa. aRniSnuli genebis
gamovlena inficirebamde an inficirebis Semdeg daavadebis mimarT
prognozirebis da prevenciis sakmaod did perspeqtivas warmoadgens.
cnobilia, rom antituberkulozur imunur pasuxSi mTavari alveolebSi
ganviTarebuli fagocituri pasuxia, sadac arsebiT rols alveoluri
makrofagebi asruleben (van Crevel et al., 2002; Adams et al., 1997). am procesebSi
CarTulia, aseve, TLR, romelic ganapirobebs organizmis imunuri pasuxis
stimulirebas da mikobaqteriis ganadgurebas (Kaufmann, 2001). Sesabamisad,
gasul aTwleulSi kvlevebis ZiriTadi nawili am procesebSi CarTuli
makrofaguri cilebis da TLR makodirebeli genebis kvlevebs moicavs
(Medzhitov, 2001; Krutzik et al, 2001; Iwasaki & Medzitov, 2004).
TLR (TLR1, 2, 4 da 6) Seicnobs sxvadasxva paTogenTan asocirebul
molekulebs (adapturi MyD88 cila) da astimulirebs Tandayolili
imunitetis ganviTarebas, citokinebis producirebas da adapturi imunitetis
process (Cook et al, 2004). maT aqvT unari, imoqmedon tol-interleikin-1-is
receptoris adaptur cilasTan (TIRAP lokalizebulia citoplazmaSi TLR2 da
TLR4 cilebis saxiT,) da moaxdinon makrofagebisa da dendrituli ujredebis
aqtivacia (Heldwein 2002; Khor et al., 2007). aRniSnuli adapturi cilis makodire-
beli genis polimorfuli variaciebi gansazRvraven organizmis gansxvavebul
midrekilebas infeqciuri daavadebebis mimarT. magaliTad, vietnamis
populaciaSi am genis TIRAPC558T*T polimorfuli variacia asocirdeba
tuberkulozur meningitTan (Hawn et al., 2006), xolo kolumbiis populaciaSi
igive polimorfuli variacia (TIRAPC558T*T) filtvis tuberkulozis mimarT
organizmis mdgradobasTan asocirdeba (Castiblanco et al., 2008).
55
infeqciuri daavadebis mimarT mgrZnobelobis ganmsazRvreli genebis
didi nawili moTavsebulia adamianis histoSeTavsebadobis mTavar kompleqs-
Si (MHC) (Medzitov, 2001). pacientebi, romlebic atareben gansazRvruli tipis
adamianis leikocituri antigenebis (HLA) II klasis alelebs, aviTareben
gansxvavebul imunur pasuxs tuberkulozis mimarT da gansxvavebulad arian
midrekilni daavadebis ganviTarebisken. HLA-s da tuberkulozs Soris
asociaciuri kavSiris Sesaswavlad sxvadasxva populaciaSi Catarebuli
kvlevebis Sedegad gamovlenilia tuberkulozisadmi genis mgrZnobelobis 10
polimorfuli variacia. (Kim et al.,2005; Freidin et al., 2006; Palomino et al., 2007; Taype et
al., 2010;).
HLA-DRB1*1501 da -DQB1*0601 alelebi tuberkulozTan asocirdeba
indoeTis Crdilo da samxreTis eTnikur populaciebSi (Ravikumar et al., 1999),
xolo -DQB1*0503 aleli - vietnamis populaciaSi (Goldfeld et al., 1998). HLA-
DQB1*05 da -DQB1*02 alelebis asociaciuri kavSiri tuberkulozTan
dafiqsirda poloneTis populaciaSi (Dubaniewicz et al., 2003). meqsikaSi - HLA-
DQA1*0101, -DQB1*0501 (Escandon et al., 1999), xolo koreaSi HLA-DRB1*0803 da -
DQB1*0601 alelebi aRmoCnda CarTuli daavadebis progresirebaSi. kanadis
mosaxleobis kvlevisas gamovlinda tuberkulozis winaswarganpirobebulobis
HLA-B8 aleli, CrdiloeT amerikis zangebSi –HLA-B5, -B15 da DR-5 aleli,
egviptelebSi - HLA- A2 da –B5, berZnebSi - HLA–B27 aleli. kvlevaTa Sedegebi
metyvelebs, rom MHC genebis polimorfizmi msoflios mraval populaciaSi
asocirdeba tuberkulozisadmi populaciis mdgradobis gaZlierebasTan
(Kim et al., 2005).
TNFα-is makodirebeli genis, romelic mTavar rols TamaSobs
tuberkulozis dros granulomis warmoqmnaSi da makrofagebis aqtivaciaSi,
lokusi ganTavsebulia MHC klasis III regionSi. bekeris (Bekker et al., 2000)
monacemebiT, TNF-α asocirdeba eqstensiur tuberkulozTan. msgavsi asociacia
eqstensiuri tipis tuberkulozTan rusul populaciebSi TNF-308 polimor-
fizmTan gamovlinda (Bikmaeva et al., 2002), Tumca, peruSi tuberkulozTan
56
aRniSnuli lokusis asociaciuri kavSiri ar iqna napovni (Ben-Selma et al., 2010;
Fan et al., 2010). selvarajis (Selvaraj et al., 2001) mier indur populaciaSi miRebuli
monacemebiT, Tu genomSi HLA-A1, -B17, -B21 da -DR7 TNF-308*A erTad iqneba,
kompleqsi ganapirobebs tuberkulozis mimarT organizmis mdgradobas da
mikobateriis inhibirebas.
rigi mecnierebis azriT, tuberkulozis winaswarganpirobebulobas
gansazRvravs gama-interferonis (IFN-γ) makodirebeli lokusebi, romelTa
produqtebi CarTulia mikobaqteriis mimarT ganviTarebul ujredul imunur
pasuxSi (Flynn, 1993; Lalvani et al, 1998; Hill et al., 2006; Taype et al., 2006).
garda zemoT aRniSnuli genetikuri lokusebisa, mecnierTa yuradReba
miipyro interleikinebis makodirebeli genebis polimorfizmsa da
tuberkulozs Soris asociaciurma kavSirma. aRniSnuli lokusebi maRali
variabelobiT xasiaTeba da xSirad specifikuria sxvadasxva eTnikuri
populaciisTvis. cnobilia, rom IL-12BR1 geni akodirebs IL- 12 receptors. igi
marokos (Remus et al., 2004; cooper et al., 2007) da iaponiis (Akahoshi et al., 2003)
populaciaSi asocirdeba filtvis tuberkulozTan da aRniSnuli lokusis
matarebel pirebSi daavadebisadmi mgrZnobeloba gazrdilia, magram genis IL-
12RB1 variacia, romelic gamowveulia erTnukleotidiani cvlilebiT, iaponur
populaciaSi ar asocirdeba daavadebasTan (Lee et al., 2005).
gambiis mosaxleoba filtvis tuberkulozisagan garkveulwilad
„daculia“ heterozigoturi IL1RNVNTR*2 (IL-1receptoris antagonisturi geni)
genuri alelis matareblobiT. aRniSnul populaciaSi Seswavlili iqna
agreTve IL1B-511 aleli, magram mikobaqteriul infeqciasTan misi asociaciuri
kavSiri ver iqna gamovlenili (Bellamy et al., 1998). sxva avtorebis mier gambiaSi
Catarebulma kvlevebma gamoavlina heterozigoturi IL1B-511*C alelis
asociacia filtvis tuberkulozTan, maSin, roca IL1B-511*C-iT homozigotur
individebSi aranairi asociaciuri kavSiri ar gamovlinda am mimarTulebiT
(Awomoyi et al., 2005). rusul populaciaSi Catarebulma kvlevebma daadastura
57
IL1RNVNTR*2 alelis maRali mgrZnobeloba filtvis tuberkulozisadmi
(Freidin et al., 2006).
belamisa da TanamSromlebis (Bellamy et al., 1998) mier napovni iqna
korelacia IL10 polimorfizmsa da filtvis tuberkulozs Soris gambiaSi.
heterozigoturi IL10-1082 da IL10-1082*G alelebis matarebloba asocirdeba
filtvis tuberkulozis mosalodnelobasTan kambojasa da TurqeTSi
Catarebuli gamokvlevebiT (Delgado et al., 2002; Ates et al., 2007). IL10-592*A -
ganapirobebs antimikobaqteriul dacvas koreis mosaxleobaSi (Shin et al., 2005),
xolo IL10-1082*A ki tuberkulozis mosalodnelobas gansazRvravs kolumbiaSi
(Henao et al., 2006). morenosa da TanamSromlebis (Moreno et al.,2007) mier
Seswavlili iqna IL10 makodirebeli genis -1082, IL10-819 da IL10-592 alelebi,
Tumca, miRebuli Sedegebi sxvadasxva eTnikur populaciaSi sakmaod
gansxvavebuli aRmoCnda.
antituberkulozur imunitetSi mniSvnelovani roli akisria
transformaciuli zrdis faqtor 1-s TGF-b1 (Moore et al., 2001), romelic
aregulirebs ujreduli zrdisa da gare matriqsis warmoqmnis procesebs da
monawileobs imunoregulaciaSi tuberkulozis dros (Wenner and Yan, 2003).
aRniSnuli genis polimorfizmi Seswavlili iqna CineTis, hong-kongis,
kolumbiisa da TurqeTis populaciebSi (Niimi et al., 2002; Henao et al., 2006; Oral et al.,
2006; Mak et al., 2007), sadac tuberkulozsa da TGFβ1+869 alels Soris
asociaciuri kavSiri ver iqna napovni, maSin, roca aRniSnuli genis TGFβ1+869*T
aleli iranul populaciaSi gansazRvravs organizmis mdgradobas
mikobaqteriuli infeqciis mimarT (Amirzargar et al., 2006).
Tvlian, rom vitamin D-s receptoris geni (VDR) raRac rols asrulebs
infeqciuri agentebis mimarT antituberkulozuri imunuri pasuxis aqtivaciaSi
(Prithvi R. et.al. 2011). sanam antituberkulozur mkurnalobaSi CaerTveboda
qimiuri preparatebi, sanatoriuli mkurnalobis ganuyofeli nawili D
vitaminiT mdidari racioni da mzis sxivebis abazanebi iyo (Evans, 1994). vitamin
D3 -is sinTezi damokidebulia kanze ultraiisferi sxivebis moqmedebaze,
58
romelSic mTavar rols pigmenti melanini asrulebs. mecnierTa varaudiT, igi
SesaZloa, garkveulwilad gansazRvravdes tuberkulozisadmi organizmis
mgrZnobelobas (Liu et al., 2006). pigmentirebul rasebSi, sadac daavadeba
gansakuTrebiT maRali prevalentobiT xasiaTdeba, SeiniSneba D vitaminis
ukmaroba, gansakuTrebiT ki - naklebadmziani klimatis pirobebSi (Wilkinson et al.,
2000). MogvianebiT gamovlenili iqna VDR-is polimorfuli variaciebi
(Uitterlinden., 2004) da dadgenil iqna aRniSnuli genis polimorfizmis
mgrZnobeloba osteoarTritis, diabetis, simsivnis da kardiovaskularuli
daavadebebis (Uitterlinden et al., 2004) da tuberkulozis mimarT (Bellamy et al., 1999).
gamovlenili iqna VDR-is FokI, TaqI, BsmI da ApaI polimorfuli alelebi
(Bornman et al., 2004). meta-analizis Sedegad gamovlinda, rom VDR-is
polimorfuli variaciebi sxvadasxva populaciaSi asocirdeba
tuberkulozisadmi mgrZnobelobasTan (Sharma et al., 2011). uilkinsonisa da
Tanaavtorebis azriT (Wilkinson et al., 2000), vitamin D-s receptori sxva genetikur
Tu garemo faqtorebTan erToblivad ganapirobebs tuberkulozisadmi
mdgradobas
radganac makrofagebi tuberkulozuri paTologiisas yvelaze metad
CarTuli ujredebia dacvis pirveli xazis SeqmnaSi, mecnierTa gansakuTrebuli
yuradReba SLC11A1 genma miiqcia.
bunebriv rezistentobasTan asocirebuli makrofaguri cilis
makodirebeli SLC11A1 genis roli tuberkulozuri infeqciis dros. geni
SLC11A11 Tavdapirvelad bcg genad iwodeboda (Skamene, 1994). igi tuberkulozis
mikobaqteriiT inficirebuli maspinZeli organizmis genetikur struqturaSi
daavadebis mimarT mgrZnobelobis Seswavlis mizniT aprobirebuli pirveli
geni iyo da napovni iqna anomalurad sensibiluri xazis BCG Salmonella da
Leishmania infeqciis mqone TagvebSi, sadac baqteriuli infeqciebisadmi
mdgradobas ganapirobebda.
SLC11A1 geni akodirebs makrofagebis membranaSi ganvlad transmembranul
cilas, romlis funqcias orvalentiani kaTionebis (Fe(2+) da Mn(2+), rogorc
59
pro- da eukariotuli katalazebisa da zeJangebis kofaqtorebi) membranuli
transporti da fagolizosomebSi ionuri statusis SenarCuneba warmoadgens,
rac Tavis mxriv, iwvevs makrofagebis aqtivacias (Nevo, 2006), maspinZlis
antimikrobuli radikalebis generalizebas da mikobaqteriis winaaRmdeg
damcavi fermentebis gamomuSavebas (Blackwell et al, 2000, 2003; Goswami et al, 2001).
tuberkulozTan SLC11A1 genis asociaciuri kavSiris Sesaxeb pirveli
eWvi mas Semdeg gaCnda, rac TagvebSi Catarebuli eqsperimentis Sedegebi
gamoaqveynes. rodesac Tagvebis erT-erT xazs gauTiSes aRniSnuli geni, isini
veluri xazebisagan gansxvavebiT iseTi rezistentulebi ar aRmoCndnen M.
tuberculosis mimarT (North et al., 1999). SLC11A1 genSi momxdari konkretuli saxis
mutacia mniSvnelovnad amcirebs fagosomebis momwifebas da asidifikacias.
amdenad, mutanturi Tagvebi ufro mgrZnobiareni aRmoCdnen tuberkulozis
mimarT (Vidal et al, 1996).
mas Semdeg, rac am genis analogi SLC11A1 geni adamianis genetikur
struqturaSic iqna napovni kanaduri ojaxis magaliTze (risk faqtori = ~ 10)
(Cellier et al., 1994) da gairkva misi polimorfizmis Zlieri asociaciuri kavSiri
tuberkulozisadmi mgrZnobelobaSi, interesi kvlav ganaxlda (Greenwood et al.,
2000).
gamovlenili iqna asociaciuri kavSiri tuberkulozis mosalodnelobasa
da SLC11A1 genetikur variaciebs Sorisac adamianTa populaciebSi (Cervino et al.,
2000; Takahashi et al., 2008). amJamad cnobilia SLC11A1 genis oTxi variacia (Bellamy
et al., 1998), romlebic yvelaze xSirad gvxvdeba tuberkulozuri infeqciebisadmi
winaswarganpirobebulobis Tu mdgradobis Seswavlis mizniT ganxorcielebul
kvlevebSi. SLC11A1 geni da misi polimorfuli variaciebi yvelaze metad
Seswavlili genetikuri faqtoria tuberkulozis SemTxvevaSi msoflios
sxvadasxva eTnikur populaciaSi (Bellamy et al., 1998; Ryu et al., 2000; Blackwell et al.,
2001; Zhang et al., 2005; Li et al., 2006; Liu et al., 2004; Abel & Casanova 2010)
bolo dros gamoqveynebuli meta-analizis SedegebiT, romelic
eyrdnoboda 17 sxvadasxva kvlevas (Li et al., 2006), naCvenebi iqna, rom SLC11A1 genis
60
4 sxvadasxva lokusSi arsebuli polimorfizmi (5’(GT)n, INT4, 3′UTR, D543N)
asocirdeba tuberkulozis mimarT organizmis mgrZnobelobasTan.
afrikis da aziis populaciebSi SLC11A1-s 3’UTR, D543N da 5’(GT)n
lokusebis polimorfizmi myarad asocirdeba filtvis tuberkulozTan.
individebi, romlebic atarebdnen aRniSnul lokusebSi, Tundac,
erTnukleotidian cvlilebas, tuberkulozis ganviTarebis 27%, 61% da 25%-iT
maRali riskis jgufebs miekuTvnebodnen aRniSnuli lokusebis Sesabamisad.
aziis polulaciebSi samive aleli ufro maRali sixSiris asociaciur kavSirSi
(39%, 59%, 65%) gamovlinda tuberkulozis mimarT, vidre sxva regionis
warmomadgenlebSi. genis zemoT CamoTvlili oTxi variaciidan mxolod 3’UTR-
is polimorfizmi araa dafiqsirebuli tuberkuloziT daavadebul afrikul
populaciaSi. rac Seexeba evropul regions, kvlevebis Sedegad Seswavlil
populaciebSi aRniSnuli oTxidan tuberkuloziT daavadebul populaciaSi
arc erTi lokusis polimorfizmi ar gamovlenila, Tumca, arsebobs varaudi
dabali sixSiriT (9.3%) misi arsebobis Sesaxeb (Li et al., 2006).
multirezistentuli tuberkulozis prevalentobis maCveneblis
zrdasTan erTad mecnierebi axali gamowvevis winaSe dadgnen (Espinal et al., 2003).
arsebuli monacemebi MDR-TB-is ganviTarebaze maspinZeli organizmis
genetikuri faqtorebis zegavlenis Sesaxeb Zalze mwiria, Tumca, msgavsi
zegavlenis arseboba sruliad SesaZlebelia. 2005 wels zangisa da misi
TanamSromlebis mier dafiqsirda, rom SLC11A1 genis polimorfizmi asocirdeba
tuberkulozis mZime formasTan (Zhang et al., 2005), xolo iaponiaSi Catarebuli
kvlevebiT am genis D543N da 30UTR lokusebSi momxdari cvlilebebi
asociaciur kavSirSia MDR-TB-Tan iaponur populaciaSi (Takahashi et al., 2008).
aRniSnulidan gamomdinare, SesaZloa, SLC11A1-s polimorfizmi gavlenas
axdendes multirezistentuli tuberkulozis SemTxvevebze.
dRes mecnierTa interesi mimarTulia tuberkulozisadmi organizmis
mdgradobis ganmapirobebeli genetikuri faqtorebisa da misi moqmedebis
61
meqanizmebis gamovlenisken. genetikuri mdgradobis faqtorebis garkvevam,
SesaZloa, axlo momavalSi migviyvanos populaciis doneze tuberkulozis
prevenciasTan bunebriv mdgradobaze pasuxismgebeli meqanizmebis
stimulirebiT.
62
Tavi II. kvlevis masala da meTodebi
II.1. kvlevis masala
kvleva Catarebuli iqna qarTuli da saqarTveloSi mcxovrebi
azerbaijanuli populaciebis tuberkuloziT daavadebul pacientebSi.
kvlevisas Seswavlili iqna filtvis tuberkulozis sxvadasxva formiT
daavadebuli 415 pacienti, romlebic Sedarebuli iqna janmrTel donorul
populaciasTan.
sakvlev masalas warmoadgenda pacientebis venuri (2ml) da
periferiuli (20mkl) sisxli. kvlevisTvis sxvadasxva etapze gamoyenebuli
iqna eriTrocituri masa, garecxili eriTrocitebi; eriTrocitebi
plazmaSi, sisxlis SratSi da fiziologiur xsnarSi; pacientis sisxlis
Srati da pacientis dnm.
sisxli Segrovili iqna randomulad orTave sqesis 17-65 wlis asakis
pacientebidan. pacientTa umravlesoba iyo kultura-dadebiTi.
kvleva ganxorcielda Semdegi mimarTulebebiT:
1. tuberkulozTan eriTrocituri jgufuri antigenebis korelaciuri
kavSiris gamosavlenad Seswavlili iqna:
- filtvis tuberkuloziT daavadebuli 203 qarTveli pacienti, (113
sxvadasxva tipis wamlis mimarT sensitiuri, xolo 90 tuberkulozis
wamlis mimarT rezistentuli formiT iyo daavadebuli). sakvlevi
jgufebis monacemebi Sedarebuli iqna donorul (janmrTel) populacias-
Tan (Nagervadze, 2010);
- 92 azerbaijaneli pacienti (53 f./tb. sensitiuri, 39 f./tb.
wamalrezistentuli formiT daavadebuli). sakvlevi masala Sedarebuli
iqna donorul (janmrTel) azerbaijanul populaciasTan (Геноф. геногеогр.
Народoнос.Т.I. 2000).
2. tuberkuloziT daavadebulTa imunuri statusis Sesaswavlad
gamokvleuli iqna 120 pacienti, romelTagan calke sakvlev jgufebad
63
gamoiyo: sensitiuri da rezistentuli tuberkulozis, daavadebis
sxvadasxva klinikuri (kerovani, infiltraciuli rRvevis fazaSi, fibro-
kavernozuli) formis mqone, aseve, pirveladi da namkurnalevi pacientebi
da Sedarebuli iqna janmrTel moxaliseebTan.
3. infeqciuri daavadebebis mgrZnobelobasTan asocirebuli SLC11A1
genis D543N lokusis polimorfizmis rezistentul tuberkulozTan asoci-
aciuri kavSiris gamosavlenad gamokvleuli iqna sul 120 pacienti (80 rezisten-
tuli da 40 sensitiuri filtvis tuberkuloziT daavadebuli pacienti).
kvlevebi ganxorcielda Semdegi laboratoriebis bazaze:
baTumis SoTa rusTavelis saxelmwifo universitetis biologiis
departamentTan arsebuli imunogenetikis saswavlo-kvleviTi laboratoria;
filtvis daavadebaTa da tuberkulozis erovnuli centris
bioqimiuri laboratoria;
aleqsandres teqnologiuri saganmanaTleblo institutis bazaze
arsebuli saswavlo-samecniero laboratoria (saberZneTi);
kompania “Bioprobe”-is samecniero-diagnostikuri laboratoria „bio-
probi“ (saberZneTi).
II.1. kvlevis meTodebi
II.1.1. imunoserologiuri meTodebi
kvlevisas viyenebdiT saerTaSorisod aRiarebul imunoserolo-giur
meTodebs (Parsons, 1985; Judd, 1994):
- АВО sistemis gansazRvris pirdapiri reaqcia monoklonuri
antisxeulebis (anti-A da anti-B) gamoyenebiT;
- rezus sistemis antigenebis gansazRvra
a) eqspres-meTodi universaluri reagentebis gamoyenebiT;
64
b) eqspres-meTodi planSetze sruli formis antisxeulebiT;
- MN da Kell sistemis antigenebis gansazRvra eqspres-meTodiT uni-
versaluri monoklonuri antisxeulebis gamoyenebiT (Voak, 1986, 1989).
muSaobisas viyenebdiT Semdegi specifikurobis mqone test-
sistemebs: anti -АВ, -В, -А, -D, -CD(G), -C, -c, -E, -Ce, -e, -K, -M, -N (Messeter et al.,
1984; Watkins et al., 1988; OОО «Гемостандарт», Москва), standartul 0(I), A(II), B(III),
AB (IV) Sratebs (gamoyenebuli reaqtivebis titri ar iyo 1:32-ze dabali)
(Voak, 1999). (sur.2-3).
sur. 2-3. sisxlis jgufebis tipireba monoklonuri antisxeulebis gamoyenebiT
II.1.2. biostatistikuri analizis meTodebi
АВ0 sistemis genebis alelebis gavrcelebis sixSires vTvlidiT
berSteinis (F.Bernstein) mier SemoTavazebuli formuliT, romelic
gamoiyeneba samaleliani genetikuri sistemis kvlevisas. I0, IА da IВ genebis
sixSire mocemul SemTxvevaSi aRniSnulia r, p da q asoebiT:
r = O
p = 1- OA
q = 1- OB
65
sadac 0, А da В – 0(I), A(II) da B(III) jgufis matarebel adamianTa
Tanafardobaa sakvlev obieqtTa saerTo raodenobasTan mimarTebaSi.
Rh sistemis genebisa da haplotipebis sixSire gamoTvlili iqna
Semdegi formulebis gamoyenebiT:
1. D = 1 - dd
2. C = 1 - cc
3. E = 1 - ee
4. c = 1 - CC
5. e = 1 - EE
6. d = 1 -√ D
sadac D, C, E, c, e genebis matarebel pirTa raodenobaa sakvlevi
masalis raodenobasTan TanafardobaSi; dd, cc, ee, CC da EE – Sesabamisi
fenotipebis sixSire. Rh haplotipebis sixSire gamoTvlil iqna mourantis
(A. E. Mourant) mier SemoTavazebuli formuliT:
1. cde = ccddee
2. Cde =cde
Ссddee
2
3. cdE = cde
ссddEe
2
4. cDe =cde
ccDee
2
5. cDE = 2cdEccDEE - сdE
6. CDe =2CdeCCDee - Сde
7. CDE=)(2 cdeCDe
CCDEe
sadac ccddee, Ccddee, ccddEe, ccDee, CCDee da ccDEE – Sesabamisi
fenotipebis sixSirea.
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RhD da Kell sistemis alelebis koncentraciis gamosaTvlelad
gamoviyeneT Semdegi formulebi:
q = N
naa ,
p= 1-q
sadac aan aRniSnuli lokusebis mixedviT recesiuli homozigotebia
(dd da kk); N - gamokvleul pirTa saerTo raodenoba.
MN sistemis alelebis koncentraciis dasadgenad Cvens mier
gamoyenebul iqna Semdegi formulebi:
P= N
nn ABA2
1
,
q = N
nn ABB2
1
sadac An – M fenotipis matarebelTa raodenobaa,
ABn - MN
fenotipebisa, xolo Bn - N fenotipis matarebelTa raodenobaa.
cdomilebebi gamoTvlil iqna formuliT:
M = (100 ) /P P n (Урбах, 1975)
sadac Р – antigenebis sixSirea % -Si, n – sakvlevi obieqtebis
raodenoba.
II.1.3. kvlevis molekulur-bioloqimiuri meTodebi
SLC11A1 genis D543N lokusis polimorfizmis Seswavlisa da filtvis
tuberkulozis multirezistentul formebTan SesaZlo asociaciuri
kavSirebis gamovlenis mizniT gamoyenebuli iqna polimeruli jaWvuri (PCR) da
restriqciuli fragmentebis sigrZis polimorfizmis (RFLP) reaqciebi.
eqsperimenti moicavda Semdeg etapebs:
67
1. dnm-is eqstraqcia;
2. praimerebis dizaini;
3. polimeruli jaWvuri reaqcia (PCR);
4. restriqciuli fragmentebis sigrZis polimorfizmi (RFLP);
5. agarozas gel-eleqtroforezi.
II.1.3.1. dnm-is eqstraqcia
dnm-is eqstraqciisTvis SerCeuli iqna “invitrogenis” mier warmoebuli
„PureLink™ Genomic DNA Kits“ kiti sisxlis nimuSebisTvis, katalogis nomriT -
K1820-01, K1820-02, K1821-04.
dnm-is gamoyofas vaxdendiT pacientebidan aRebuli 200 mkl venuri
sisxlidan (sur. 4-5).
sasurveli raodenobis dnm-is misaRebad SevarCieT meTodika, romelic
moicavs Semdeg Tanmimdevrul procedurebs:
I. lizatas momzadeba, - ujredebis lizisi
- sterilur epindorfebSi vaTavsebdiT 200 mkl sisxls;
- vamatebdiT proteinkinaza K 20 mkl;
- vamatebdiT rnm-azas 20 mkl-s;
- narevs frTxilad vurevdiT da vaCerebdiT 2 wT inkubaciisTvis;
- vamatebdiT 200 mkl PureLink™ genomur lizisur/SemboWav bufers da
vurevdiT homogenuri masis miRebamde;
- vaCerebdiT 10 wuTis ganmavlobaSi 55°C-ze wylis abazanaSi;
- vamatebdiT 200 mkl 96-100% eTanols da vanjRrevdiT ~5 wm homogenuri
siTxis miRebamde.
Semdeg etapze gamoviyeneT:
lizata;
steriluri 1.5 ml-iani mikrocentrifugis sinjarebi;
mikrocentrifuga - 10 000 brunze maRali sixSiris;
68
steriluri wyali - pH 7.0-8.5 an damleqavi buferi;
PureLink™ genomuri gamrecxi buferi - 1 da 2;
PureLink™ genomuri gamomleqi buferi;
PureLink™ filtriani svetebi;
PureLink™ plastikuri sinjarebi filtriani svetebis mosaTavseblad;
II. dnm-is SeboWva - am etapze lizata muSavdeba specifikuri dnm-is
SemboWveli buferiT:
- dnm-is Semcveli lizata gadavitaneT filtrian svetSi (~640mkl);
- davamateT PureLink™ genomis lizisuri/SemboWveli buferi;
- davacentrifugeT 10 000 brunze 1wT-is ganmavlobaSi;
- gafiltruli siTxe gadavRvareT, filtriani sveti gadavitaneT axal
mikrocentrifugis sinjaraSi.
-
sur. 4-5 dnm-is eqstraqciis procesi.
III. dnm-is garexcva: dnm vrecxavdiT ori tipis (1 da 2) gamrecxi xsnariT.
isini uzrunvelyofen dnm-is Semcveli lizatidan ujredis komponentebis
narCenebis da rnm-is Camocilebas. sinjaris filtrian svetSi vasxamdiT 500 mkl
gamrecx bufers-1 da vacentrifugebdiT 10 000 brunze 1wT-is ganmavlobaSi,
oTaxis temperaturaze;
- gafiltrul siTxes vRvridiT, filtriani svetebi gadagvqonda axali
mikrofugis sinjaraSi;
69
- vamatebdiT 500 mkl gamrecx bufers-2, vacentrifugebdiT 3 wT-is
ganmavlobaSi, maqsimalur siCqareze oTaxis temperaturis pirobebSi.
IV. dnm-is gamoleqva - sinjaris filtris mier SeboWili dnm-is gamoleqva
movaxdineT specifikuri gamomleqi buferis saSualebiT. gamoviyeneT
gamoleqvis ori etapi: pirveli 100 mkl (dnm-is gamosavlianoba 80-85%), xolo
meore - 50 mkl moculobiT (gamosavlianoba 10-15%).
dnm-is raodenobis gansazRvra da misi ganzaveba. dnm-is eqstraqciis
Semdeg misi raodenobis gansazRvrisTvis gamoyenebuli iqna ultraTa-
namedrove, srulspeqtriani (220-750 nm) speqtrofotometri Nano-Drop ND-1000
(sur. 6-7).
sur. 6-7. dnm-is raodenobis gansazRvra
polimerazuli jaWvuri reaqciis gansaxorcieleblad SerCeuli iqna dnm-
is optimaluri koncentracia 10 ng/mk.l-ze, risTvisac TiToeuli saanalizo
nimuSi ganvazaveT tris acetatis edta-s (eTilendiamintetraacetatis mJava)
(TAE) gamoyenebiT. sasurvel koncentraciamde ganzavebisTvis gamoviyeneT
torsiuli kalkulatori, romelic damyarebulia moculobisa da
koncentraciis Semdeg principze:
C1V1 = C2V2 V2 = C1V1 / C2
sadac C1 da V1 aris saanalizo nimuSis/xnaris sawyisi koncentracia da
moculoba, xolo C2 da V2 saanalizo nimuSis saboloo moculoba da
koncentracia.
70
II.2.3.2. praimerebis dizaini
genTa eleqtronuli bazidan (NCBI) aviReT SLC11A1 genis (2q 36.1)
nukleotiduri Tanmimdevroba da davgegmeT D543N lokusis (me-15 egzoni)
SeswavlisTvis saWiro praimerebi standartuli wesebis Sesabamisad (Innis and
Gelfand, 1991):
Sinaarsiani praimeri: 5´GTGAGACGACAGACAAATGTAGT3´
uSinaarso praimeri: 5´GGTACCGTCCAGCTGAGA3´
II.2.3.3. polimeruli jaWvuri reaqcia
PCR optimizacia
dnm-is amplificirebisTvis gamoviyeneT polimeruli jaWvuri reaqcia
(PCR). sakvlevi nimuSebis dnm-is sasurveli raodenobis misaRebad movaxdineT
PCR reaqciis standartuli protokolis modificireba/ optimizacia.
optimizaciis pirvel etapze SevarCieT reaqciisTvis saWiro reagentebis
optimaluri koncentraciebi. reaqciis moculoba Seadgenda 20 mk.l-s TiToeuli
saanalizo nimuSisTvis.
reagentebi raodenoba (mkl)
buferi 2
nukleotidebis narevi 2
praimerebis narevi 0,8
ormagad distilirebuli H20 6,1
Taq polimeraza 0,1
MgCl2 6
dnm 3
20 mk.l
PCR-is optimizaciis Sedegad SevarCieT amplifikaciisTvis yvelaze
xelsayreli pirobebi dnm-is saWiro raodenobis misaRebad:
71
PCR reaqciis Semdeg amplificirebuli dnm-is nimuSebs vuSvebdiT agarozas
gelis eleqtroforezze da vamowmebdiT transiluminatorSi (sur.8).
sur. 8. PCR produqti gelze
II.2.3.4. restriqciuli fragmentebis sigrZis polimorfizmi (RFLP)
SLC11A1 genis D543N lokusis polimorfizmis gamosavlenad
amplificirebuli dnm-is nimuSebi restriqciuli fragmentebis sigrZis
polimorfizmis meTodis (RFLP) gamoyenebiT damuSavda NEB-is (new England
Biolabs) restriqciuli fermentiT - Hpy188I, romelic saZiebel regionSi axdens
AG da GG nukleotiduri wyvilebis Secnobas da maT Soris arsebuli
wyalbaduri da kovalenturi bmebis gaxleCas, ris Sedegadac miiReba dnm-is
fragmentebis sigrZis polimorfizmi (sur.9):
sur.9. Hpy 188I-is restriqciuli saiti
940C → 2 wT
denaturacia 940C → 20 wm
gamowva 560C → 30 wm 40 cikli
elongacia 720C → 20wT
720C → 2 wT
72
optimizaciis gziT SevarCieT fermentis aqtivaciisTvis saukeTeso
porobebi. RFLP reaqciis moculoba Seadgenda 50 mkl-s:
reagentebi moculoba (µl)
amplificirebuli dnm 10
restriqtaza - Hpy 188I 1
10xNEB buferi 1
ormagad distil. H2O 38
50 µl
reaqcia ganxorcielebuli iqna wylis abazanaSi 370C-ze erTi saaTis
ganmavlobaSi inkubirebiT. inkubaciis Semdeg fermentis deaqtivaciisTvis
sakvlev masalas vaCerebdiT 800C-ze 20 wuTis ganmavlobaSi. Semdgom etapze
saanalizo masalas vRebavdiT da vamowmebdiT gel-eleqtroforeziT.
II.2.3.5. agarozas gel-eleqtroforezi
eleqtroforezisTvis viyenebdiT Cveulebriv agarozas da maRali
mgrZnobelobis ultra - sufTa „agaroza 1000“-s. SerCeuli iqna gelis
optimaluri simkvrive, buferuli sistemebi, gelis saxeoba da sisqe.
eleqtroforezis buferad viyenebdiT tris-boratis edtas (TBE).
eleqtroforezisTvis viyenebdiT agarozas 2%-an gels; dnm-s
vizualizacisTvis agarozas gelze vamatebdiT fluorescenciul eTidiumis
bromidis 0.5 mkg/ml saRebavs gelis yovel 100 ml-Si winaswar SetaniT. gelze
vuSvebdiT amplificirebuli dnm-is 10 mkl 5 mkl saRebavTan erTad. dnm-is
sazomad viyenebdiT 100 n.f. standarts. eleqtroforezi grZeldeboda 1 sT-is
ganmavlobaSi 110v Zabvaze. eleqtroforezis dasrulebis Semdeg gels
73
vamowmebdiT ultraiisferi sxivebis qveS transiluminatorSi (Bio-Rad) (sur.
10-11).
sur. 10. gel-eleqtroforezi sur. 11. dnm-is vizualizacia agaroza . 1000-is gelze
II.2.4. imunologiuri analizis meTodebi
tuberkuloziT daavadebul pacientTa imunuri statusis dasadgenad
gamoyenebuli iqna imunoturbidometruli da imunofermentuli analizis
meTodebi, romelTa saSualebiT gamovlenili iqna antituberkulinuri jamuri
da imunoglobulinebis (IgA, IgM, IgG) saerTo done tuberkuloziT daavadebul
pacientTa sakvlev nimuSebSi.
II.2.4.1. imunoturbidometruli meTodi
TiToeuli pacientis sakvlev nimuSSi (sisxlis Srati) arsebuli
calkeuli imunoglobulinis - IgA, IgM, da IgG-s saerTo donis gamovlena moxda
imunoturbidometruli meTodiT bioqimiuri analizatoris - Humalyser 2000-is
gamoyenebiT.
calkeuli imunoglobulinisTvis (IgA, IgM, IgG) imunoturbidometrSi
movaxdineT dakalibreba standartuli kalibratorebis gamoyenebiT, romelTa
sakalibro mrudzec moxda sakvlevi pacientebis nimuSebis wakiTxva.
74
kalibraciisas gamoyenebuli iqna:
5 kalibratori+1 nulovani 10 mkl
buferi 500 mkl
anti IgA, IgM, IgG Srati 500 mkl
imunoturbidometruli analizisÈmeTodiÅmoicavda reagentebs Semdegi
TanafardobiT:
reagentebi moculoba mk.l
buferi 500
antiSrati 500
sakvlevi nimuSi 10
1010 mk.l
procedura:
8,5%–ian polieTilenglikolis (pH-7,2) Semcvel tris-buferSi vazavebdiT
standartul xsnarebs (kalibratorebi) da sakvlev nimuSebs. TiToeul
sinjaras vamatebdiT antiglobulinur xsnars, romelic Sedgeboda tris-
buferisa da cxvris antiSratisagan, TiToeuli imunoglobulinisaTvis (anti–
IgA, anti–IgG, anti–IgM) - cal-calke, vainkubirebdiT 370C-ze 10 wT-is ganmav-
lobaSi. kalibratorebi da nimuSSi arsebuli imunoglobulinebi iwvevdnen
aglutinacias anti–adamianis imunoglobulinTan reagentis antiSratSi.
aglutinaciis xarisxi sakvlevi pacientis nimuSi-imunoglobulinebis
koncentraciis proporciuli iyo da isazRvreboda turbidometrulad.
Sedegebs viTvlidiT speqtrofotometrulad 340 nm talRis sigrZeze
HUMALYSER 2000-is aparatiT (sur. 12):
sur. 12. HUMALYSER 2000
75
II.2.4.2 imunofermentuli analizis meTodi
SratSi specifikuri antituberkulinuri jamuri antisxeulebis
(IgM+IgG+ IgA) gamosavlenad gamoyenebuli iqna arapirdapiri imunofermentuli
analizi (ELISA).
analizi tardeboda 96-fosoian brtyelZirian planSetze, romlis
fskerzec winaswar datanili iyo antituberkulinuri antisxeulebi.
reaqciisTvis gamoyenebuli iqna:
96-fosoiani planSeti, romelzec datanili iyo specifikuri
antituberkulinuri antigeni;
nimuSebis gasazavebeli siTxe PBS/BSA (karbonat-bikarbonatuli
xsnari) da buferuli, romelic Seicavs < 0.1 % NaN3;
ferment–koniugati HRP-moniSnuli anti–adamianis Txis IgG /-IgM /-IgA;
substrat - qromogeni (3, 3’, 5, 5’ tetrameTilbenzidini);
gamrecxi xsnari (10 x koncentrirebuli) PBS/Tween;
6 standartuli kalibratori;
mablokirebeli xsnari -M0.5 M gogirdmJava.
procedura:
1. mikroplanSetis pirvel fosos vtovebdiT cariels, xolo
meoredan meSvide fosoebSi vaTavsebdiT 50 mkl sakalibro xsnarebs,
koncentraciis zrdadobis mixedviT, xolo danarCen fosoebSi - winaswar
ganzavebul sakvlev nimuSebs (Sratebs) 50 mkl moculobiT. nimuSebs
vazavebdiT 1:101 karbonat-bikarbonatuli (kbb) buferiT, romelic
Seicavda 1%-ian kazeins. misi saSualebiT vaxdendiT fosoebis
blokirebas araspecifikuri dakavSirebebis Tavidan asacileblad;
76
2. planSets vafarebdiT specialur saizolacio polieTilenis
naWers da vainkubirebdiT oTaxis temperaturaze (250C-ze) erTi saaTis
ganmavlobaSi;
3. inkubaciis Semdeg Sratidan araspecifikurad dakavSirebuli
komponentebis mosacileblad mikroplanSets vrecxavdiT xuTjer
fosfaturi buferiT, romelic Seicavda 0.05% Tween-20 xsnars, risTvisac
TiToeul fosoSi vamatebdiT 400 mkl moculobis gamrecx xsnars;
4. garecxvis proceduris Semdeg planSetis TiToeul fosos
(pirvelis garda) vamatebdiT 100 mkl winaswar gansxavebul tute-
fosfatazaTi moniSnul anti–adamianis winaaRmdeg mimarTul
antisxeulebs anu koniugatis xsnars da vainkubirebdiT 30 wuTis
ganmavlobaSi oTaxis temperaturaze;
5. inkubirebis Semdeg kvlav vrecxavdiT gamrecxi xsnariT xuTjer;
6. SratSi antimikobaqteriuli antisxeulebis arsebobis
SemTxvevaSi, tute fosfatazaTi moniSnuli anti–adamianis antisxeulebi
ukavSrdebodnen planSetis fosoebs;
7. bolo etapze fermentuli reaqciisTvis TiToeul fosoSi
(kontrolis CaTvliT) vasxamdiT 100 mkl substrats, romelic Seicavda
MgCl2 da p-nitrofenilfosfatids karbonat-bikarbonatul buferSi.
sakvlevi antisxeulebis raodenoba dakavSirebuli koniugatis raodeno-
bis proporciuli iyo. is ganisazRvreboda fosfatazas fermentuli aqtivobiT,
rac substratTan urTierTqmedebisas mas yviTlad Rebavda. es registrirdeba
speqtrofotometrulad. optikuri simkvrive izomeboda speqtrofotometr
„Humareader Single”-ze (germania) 450 nm talRis sigrZeze. analizi tardeboda
“Вектор Бест”-is firmis komerciuli reaqtivebis nakrebiT. dublikatebisaTvis
vTvlidiT saSualo ariTmetikuls.
77
Tavi III. kvlevis Sedegebi
III.1. filtvis tuberkulozis sensitiuri da wamalrezistentuli formebis asocireba АВ0, Rh-
Hr, Kell, MN sistemis eriTrocitur jgufur antigenebTan
qarTul populaciaSi
100 welze meti gavida mas Semdeg, rac dadgenili iqna, rom gansxvavebul
rasebsa da eTnosebs tuberkulozis mimarT gansxvavebuli mgrZnobeloba
axasiaTebT da radgan mgZnobelobis gansxvavebul faqtorebs atareben
(Budd,1867). saqarTvelos teritoriaze mcxovrebi eTnikuri jgufebi am dromde
Seswavlili ar iyo. Cvens mier pirvelad iqna gamokvleuli imunogenetikuri
markerebis gavrcelebis Taviseburebani [eriTrocituri jgufuri sistemebis
(АВ0, Rh-Hr, Kell, MN) antigenebi, feno- da genotipuri jgufebi, alelebi da
haplotipebi] filtvis tuberkuloziT daavadebul qarTul populaciaSi.
kvlevis pirvel etapze SevecadeT, dagvedgina filtvis tuberkulozur
(yvela tipis tuberkulozi) daavadebasTan zemoxsenebuli imunogenetikuri
markerebis asociaciuri kavSirebi. filtvis tuberkuloziT daavadebuli yvela
pacientis monacemi damuSavebuli iqna statistikuri analizis meTodebiT
daavadebisadmi mgrZnobiare fenotipebis, alelebis Tu haplotipebis
gamosavlenad da Sedarebuli iqna janmrTel (donorul) populaciasTan.
miuxedavad imisa, rom tuberkuloziT daavadebul pacientebSi sisxlis
eriTrocituli jgufuri antigenebis gavrceleba sakmaod kargadaa
Seswavlili msoflios populaciebSi, informacia daavadebis sensitiuri da
rezistentuli formebis eriTrocitur jgufur antigenebTan asociacirebis
78
Sesaxeb samecniero literaturaSi TiTqmis ar moipoveba. Seuswavlelia
saqarTveloSi mcxovrebi sxvadasxva eTnikuri warmoSobis pacientebic. amitom,
kvlevis meore etapze pacientebi dayofili iqna or - wamlis mimarT sensitiur
da wamalrezistentul sakvlev jgufebad. Seswavlil iqna eriTrocituri
jgufuri antigenebis gavrcelebis Taviseburebebi TiToeul sakvlev jgufSi.
sisxlis ABO sistemis jgufuri antigenebis mixedviT daavadebuli
populaciis kvlevisas miRebuli Sedegebis statistikuri damuSavebis Sedegad
gamovlinda sisxlis O(I) (55.5%±3,4) fenotipuri jgufis maRali sixSire
tuberkuloziT daavadebul populaciaSi, sxva jgufebTan SedarebiT maRali
sixSiriT gvxvdeba B(III) (12%±2,2) fenotipuri jgufi. xolo donorebSi
maRali sixSiriT A(II) (36%±5.1) fenotipuri jgufi aris warmodgenili
(diagr.4). am mxriv aRniSnuli monacemi emTxveva rigi sxva avtorebis monacemebs
(Platonova, 1997; Nagervadze et al., 2006).
diagr. 4. ABO sistemis fenotipuri jgufebis gavrcelebis Taviseburebani filtvis tuberkuloziT daavadebul da janmrTel qarTul populaciaSi
daavadebis sensitiur formaSi dafiqsirda O(I) (57.5±4,6) da B(III) (13.4±1,0)
fenotipuri jgufebis sagrZnoblad maRali sixSire donorebTan (O(I)-47,6±5,3;
B(III)-11,4±3,3) SedarebiT. wamalrezistentuli tuberkulozis SemTxvevaSi
0
10
20
30
40
50
60
70
0(I) A(II) B(III) AB(IV)
ფ.ტბ.
დონორი
79
maRali sixSiriT mxolod O(I) fenotipuri jgufi (51,1±5,2) dafiqsirda, xolo
B(III) jgufis SemTxvevaSi ar gamovlinda korelacia (diagr.5).
aqedan gamomdinare, SeiZleba iTqvas, rom sensitiuri tuberkuloziT
daavadebuli O(I) da B(III) jgufis fenotipis, xolo wamalrezistentuli formis
SemTxvevaSi ki mxolod O(I) fenotipuri jgufis matarebeli individebi
warmoadgens daavadebis maRali riskis jgufebs.
diagr. 5. ABO sistemis fenotipuri jgufebis gavrcelebis Taviseburebani rezistentuli da sensitiuri tuberkuloziT daavadebul da janmrTel qarTul populaciaSi
zemoT aRniSnuli fenotipuri jgufebis sixSiris maRali maCvenebeli
(1.207-jer maRali sensitiur da 1.07-jer maRali wamalrezistentul formaSi)
tuberkuloziT daavadebul populaciaSi donorebTan SedarebiT,
SesaZlebelia, gamowveuli iyos qarTuli populaciisTvis damaxasiaTebeli
TaviseburebiT.
imunoserologiuri analiziT miRebuli Sedegebis statistikuri
kvlevis meTodebiT damuSavebis Sedegad gamoTvlili iqna ABO sistemis
fenotipTa makodirebeli r(O), p(A) da q(B) alelebis sixSire.
kvlevis Sedegad dafiqsirda r(O) alelis sarwmunod maRali (0,739)
koncentracia filtvis tuberkuloziT daavadebulebSi donorul
0
10
20
30
40
50
60
70
0(I) A(II) B(III) AB(IV)
სენსიტ.ტბ
რეზისტ.ტბ
დონორი
80
populaciasTan SedarebiT, sadac aRniSnuli alelis sixSire 0,69-is tolia da
igi 1,07-jer naklebia daavadebul populaciasTan SedarebiT. rac Seexeba p(A)
alels, igi TiTqmis Tanabari sixSiriTaa daavadebul da donorul
populaciaSi. q(B) alelis maRali (0,23) sixSire donorul populaciaSia
warmodgenili, xolo daavadebulSi ki 1.24-jer naklebia (0,18) (diagr. 6):
diagr. 6. ABO sistemis antigenebis makodirebeli alelebis gavrcelebis Taviseburebani filtvis tuberkuloziT daavadebul da janmrTel populaciaSi
msgavsi maCvenebeli dafiqsirda daavadebis orive formis dros.
rogorc sensitiur, ise wamalrezistentul pacientebSi maTi gavrcelebis
sixSire TiTqmis Tanabaria. sensitiuri tuberkulozis dros r alelis
koncentracia 1,11-jer (0.75), xolo wamalrezistentuli tuberkulozis dros
ki 1.05-jer maRali (0.71) aRmoCnda donorebTan SedarebiT, sadac aRniSnuli
alelis gavrcelebis maCvenebeli 0.67-is tolia (cxr.1).
miRebul monacemebze dayrdnobiT, damajereblad SeiZleba iTqvas, rom
filtvis tuberkulozi asociaciur kavSirSi imyofeba me-9 qromosomaSi (9q34.1-
34.2) arsebul genur lokusTan, romelic gansazRvravs sisxlis ABO sistemis
fenotipebs. kvlevis Sedegebidan gamomdinare, sensitiuri tuberkulozisadmi
maRali sensibilobis jgufs miekuTvneba ABO sistemis sisxlis O(I) an B(III)
0
0,2
0,4
0,6
0,8
r p q
0,739
0,085
0,185
0,67
0,09
0,23
ფ.ტბ. დონორი
81
fenotipuri jgufis da r alelis matarebeli individebi. xolo rezistentuli
tuberkulozis SemTxvevaSi ki sisxlis O(I) fenotipuri jgufis da r alelis
matareblebi.
genetikuri sakvlevi obieqtebi
markerebi alelebi sensitiuri wamal.rezist. donorebi
tb. tb.
ABO r 0.75 0.71 0.67
p 0.09 0.09 0.09
q 0.17 0.22 0.23
n= 90 n=113 n=485
cxrili 1. ABO sistemis fenotipebis makodirebel r, p, q alelTa sixSire filtvis sensitiuri da wamalrezistentuli tuberkuloziT daavadebul da janmrTel populacaSi.
ABO sistemis A(II) fenotipuri jgufi da q alelis matarebloba,
garkveulwilad, SeiZleba miviCnioT tuberkulozis mimarT mdgradobis
ganmapirobebel faqtorad.
saintereso Sedegebi iqna dafiqsirebuli rezus (Rh-Hr) sistemis
antigenebis kvlevisas. kvlevis Sedegebze dayrdnobiT gamovlenili iqna
tuberkulozis mimarT maRali mgrZnobelobis fenotipebi da maTi makodirebeli
haplotipebi.
rogorc me-7 diagramidan Cans, tuberkuloziT daavadebulebSi
donorebTan SedarebiT (78±3,5%) 1,06-jer maRali sixSiriT gamovlinda rezus-
dadebiTi fenotipi (83±2.6%).
82
diagr. 7. Rh fenotipebis gavrcelebis Tavisebureba filtvis tuberkuloziT daavadebul da janmrTel populaciaSi
msgavsi Sedegebi gamoikveTa rezistentuli da sensitiuri tuberkulozis
SemTxvevebSic (diagr.8):
diagr.8. Rh fenotipebis gavrcelebis Tavisebureba sensitiuri da rezistentuli tuberkuloziT daavadebul da janmrTel populaciaSi
Rh+ fenotipis SedarebiT maRali sixSire gansakuTrebiT senstitiuri
tuberkuloziT daavadebul sakvlev jgufSi gamoikveTa. aq misi sixSire 1.07-jer
maRali (84±3,4%) aRmoCnda, vidre donorebSi (78±3,5%).
0
10
20
30
40
50
60
70
80
90
Rh+ Rh-
ფ.ტბ.
დონორი
0
10
20
30
40
50
60
70
80
90
100
სენსიტიური რეზისტენტ. დონორი
Rh+
Rh-
83
Rh+ fenotipis maRali sixSire daavadebul populaciaSi saSualebas
gvaZlevs, rom filtvis tuberkulozisadmi mgrZnobiare fenotipad moviCnioT
rezus-dadebiTi faqtori.
rezus sistemis alelTa ( Rh-C, Rh-c, Rh-D, Rh-E, Rh-e) sixSiris Seswavlis
mizniT, Catarebuli eqsperimentis Sedegad gamovlenili iqna garkveuli
asociaciuri kavSirebi daavadebis, rogorc wamalrezistentul, ise
sensitiur formebTan mimarTebaSi (diagr. 9, cxr. 2).
diagr. 9. Rh sistemis alelebis (E,e,C,c,D) gavrceleba tuberkuloziT daavadebul da donor populaciaSi
rogorc me-9 diagramidan Cans, janmrTeli populaciisagan gansxvavebiT,
filtvis tuberkuloziT daavadebulebSi gamoikveTa sakmaod myari korelacia
RhD, RhC da RhE alelebTan.
yvelaze maRali sixSiriT pacientebSi Rh-E (0,21) aleli dafiqsirda.
kerZod, misi sixSire 1.90-jer maRali iyo, vidre donorebSi (0.11).
daavadebulebSi, aseve, maRali aRmoCnda Rh-C alelis gavrcelebis sixSirec,
romlis maCvenebeli 0,37-is tolia, maSin, roca donorebSi 0,28-s utoldeba.
rac Seexeba rezus sistemis yvelaze Zlieri imunogenurobis Rh-Dalels, igi
daavadebul populaciaSi 1.05-jer meti sixSiriT (0,57) dafiqsirda, maSin roca
0,57
0,37
0,83
0,21
0,79
0,54
0,28
0,74
0,11
0,87
D
C
c
E
e
ფ.ტბ. დონორი
84
donorebSi ki Rh-d aleli metadadaa gavrcelebuli. igi 1.72-jer maRali
sixSiriT gvxvdeba donorebSi (diagr.9).
rezus sistemis alelTa gavrcelebis sixSire Seswavlili iqna
daavadebis orive formaSic (cxr.2):
genetikuri sakvlevi populaciebi
markerebi alelebi sensitiuri rezistentuli donorebi
tb. tb.
Rh-Hr D 0,58 0.56 0.54
C 0,42 0.32 0.28
c 0,71 0.75 0.74
E 0,20 0.22 0.11
e 0,82 0.77 0.87
n= 90 n=113 n=485
cxr. 2. Rh sistemis alelebis gavrcelebis sixSire sensitiuri da rezistentuli tuberkuloziT daavadebul da donorul populaciaSi
kvlevis Sedegebis damuSavebisas rezus sistemis alelebTan
gansxvavebuli korelacia gamoikveTa sensitiuri da wamalrezistentuli
tuberkulozis dros. senstiuri tuberkulozisadmi SedarebiT ufro metad
mgrZnobiare Rh-D (0,58) da Rh-C (0,42) alelebi aRmoCnda, xolo rezistentuli
tuberkulozisadmi ki Rh- E (0,22) aleli, xolo rezus sistemis recesiuli
alelebis SemTxvevaSi aseT kavSiri ar vlindeba.
rezus sistemis Rh-c da Rh-e alelebs, isini maRali gavrcelebiT mxolod
donorebSi gamovlinda. aqedan gamomdinare, rezus sitemis dominanturi Rh-D,
Rh-C da Rh-E alelebi mkacrad korelirebs filtvis tuberkulozTan.
85
rezus sistemis antigenebis gavrcelebis Seswavlis mizniT,
Catarebuli kvlevis Sedegebis mixedviT, tuberkuloziT daavadebul
populaciaSi gamovlinda C (60,09±3,43%) da gansakuTrebiT E (36,94±3,3%)
antigenis sixSiris maRali maCveneblebi (diagr.10).
diagr. 10. Rh sistemis antigenebis gavrcelebis procentuli maCveneblebi tuberkuloziT daavadebul da donorul populaciaSi
kvlevis Sedegebi wamalrezistentuli da sensitiuri tuberkulozis
SemTxvevaSi naCvenebia me-11 diagramaze. unda aRiniSnos, rom E antigenis
procentuli maCvenebeli RhE alelis koncentraciis Sesabamisad, maRali
sixSiriT dafiqsirda wamalrezistentuli (38,8±5,1%) tuberkulozis
SemTxvevaSi, sensitiur (35,3±4,4%) da sakontrolo jgufTan (20±4,0%) SedarebiT.
C antigeni mniSvnelovnad maRali sixSiriT sensitiuri tuberkulozis
SemTxvevebSi gamovlinda. misi procentuli maCvenebeli 65,4±4,4%-s Seadgens,
maSin, roca wamalezistentuli tuberkuloziT daavadebulebSi 53,3±5,2%-s,
xolo donorebSi 51±4,9%-s.
0
20
40
60
80
100
120
D C c E e
ფ.ტბ. %
დონორი %
86
diagr.11. Rh sistemis antigenebis gavrcelebis sixSire sensitiuri da rezistentuli tuberkuloziT daavadebul da donorul populaciaSi
filtvis tuberkulozTan asociaciuri kavSiris gamovlenis da maRali
sensibilobis jgufebis gamoyofis mizniT, aseve, Seswavlili iqna rezus
sistemis haplotipebi. am mizniT gamokvleuli iqna Rh-Hr sistemis 7 haplotipuri
cde, Cde, cdE, cDe, cDE, CDe, CDE jgufi da miRebuli Sedegebi Sedarebuli iqna
donorul populaciasTan.
aRsaniSnavia, rom cde, cDe, CDe da cDe haplotipebi, sxva iSviaT
haplotipebTan SedarebiT, zogadad maRali gavrcelebiT xasiaTdeba janmrTel
qarTul populaciaSi. analogiuri Sedegebi miviReT daavadebulTa populaciis
analizis Sedegad. aqve unda aRiniSnos, rom daavadebul populaciaSi rezus
sistemis zogierTi iseTi haplotipis gavrceleba gamoikveTa, romlebic
janmrTelebSi TiTqmis ar fiqsirdeba (diagr.12).
0
20
40
60
80
100
120
D C c E e
სენსიტიური%
რეზისტენტ. %
დონორი %
87
diagr. 12. Rh-Hr sistemis haplotipebis gavrcelebis Taviseburebani tuberkuloziT daavadebulebsa da donorebSi
kvlevis Sedegebis mixedviT filtvis tuberkuloziT daavadebuli
pacientebis qarTul populaciaSi Rh-cdE haplotipi 0,063 sixSiriTaa
gavrcelebuli. maSin, roca es haplotipi donorebSi saerTod ar gvxvdeba da
misi gavrcelebis maCvenebeli 0-s utoldeba. Cde haplotipis sixSire
daavadebulebSi 2,0-jer maRali aRmoCnda, vidre donorebSi, xolo CDe
haplotipi daavadebul populaciaSi donorebTan SedarebiT 1.05-jer maRali
sixSiriT dafiqsirda. rogorc me-12 diagramidan Cans, daavadebis mimarT
SedarebiT mdgradi aRmoCnda cde, cDe, cDE haplotipebi, romelTa gavrceleba
donorul populaciaSi gacilebiT maRalia.
aqedan gamomdinare, SeiZleba iTqvas, rom Cde, cdE da CDe haplotipebis
matarebeli individebi tuberkulozis ganviTarebis maRal risk-jgufs
miekuTvneba, xolo daavadebisadmi mdgrad jgufad cde da cDE haplotipebis
matarebeli individebi SeiZleba CaiTvalos.
rezus sistemis haplotipebis SeswavliT daavadebis wamalrezistentul
da sensitiur formebSi gamoikveTa gansxvavebuli korelaciuri kavSirebi,
rogorc daavadebis formebsa da haplotipebs Soris, aseve donorul
populaciasTan mimarTebaSi (cxr.3):
0,39
0,012
0,0063
0,13
0,07
0,2
0,004
0,436
0,006
0
0,148
0,126
0,192
0,004
0% 20% 40% 60% 80% 100%
cde
Cde
cdE
cDe
cDE
CDe
CDE
ფ.ტბ.
დონორი
88
genetikuri sakvlevi populaciebi
markerebi haplotipebi sensit. wamal.rezist. donorebi
tb. tb.
Rh-Hr cde 0,37 0.421 0,436
Cde 0 0.01 0.006
cdE 0,01 0 0
cDe 0,11 0.14 0.148
cDE 0,01 0 0,126
CDe 0,28 0.22 0.192
CDE 0 0,01 0,004
cxr. 3. Rh-Hr sistemis haplotipebis gavrceleba tuberkulozis rezistentul da sensitiur
formebSi da donorebSi
Rh-Cde haplotipi dafiqsirda mxolod wamalrezistentuli tuberkulo-
zis SemTxvevaSi, maSin, roca misi koncentracia sensitiur tuberkulozSi 0-s
utoldeba, xolo donorebSi ki 1,66-jer dabalia. filtvis tuberkulozis
sensitiuri formiT daavadebul sakvlev populaciaSi 0,01 sixSiriT
dafiqsirda cdE haplotipuri jgufi. rezus sistemis es haplotipi praqtikulad
ar gamovlenila donorul populaciasa da daavadebis wamalrezistentuli
formis pacientebSi.
samive dominanturi alelis matarebeli RH-CDE haplotipi sensitiuri
tuberkulozis dros ar gamovlenila, xolo rezistentul tuberkulozSi 0.01
koncentraciiT dafiqsirda, maSin, roca donorebSi misi maCvenebeli mxolod
0.004-is tolia.
aRniSnuli faqtidan gamomdinare, SeiZleba vivaraudod, rom
tuberkulozis rezistentuli forma asociaciur kavSirSia Cde da CDE
haplotipebTan, xolo daavadebis sensitiuri forma ki - cdE da CDe
haplotipebTan. SesaZloa, aRniSnuli haplotipebis mqone individebi
89
inficirebis SemTxvevaSi gansxvavebulad daeqvemdebaron daavadebis sensitiur
an rezistentul formas.
vinaidan cDE, cDe da cde haplotipebi mniSvnelovnad dabali sixSriT
gamovlinda daavadebul populaciaSi, savaraudod, isini ganapirobeben
daavadebis mimarT organizmis mdgradobas da maTi matarebloba erTgvar
damcvelobiT faqtorad SeiZleba miviCnioT.
Rh sistemis genotipebis kvlevisas daavadebulebSi SedarebiT maRali
sixSiriT gamovlinda Cc (52,21±4,2%) da igi 1.12-jer aRemateboda donoruls.
mniSvnelovnad maRali iyo EE (4,4±1,4%) da Ee (32,51±3,2%) genotipebis sixSire. EE
genotipi 2-jer, xolo Ee 1.69-jer aRemateba daavadebul populaciaSi mis
gavrcelebas. ee genotipi ki 1.22-jer dabali sixSiriT aris warmodgenili
(63±%) daavadebulebSi donorebTan (77,4±4,4%) SedarebiT (diagr.13).
diagr. 13. Rh-Hr sistemis genotipebis gavrcelebis Tavisebureba tuberkuloziT daavadebul da donorul populaciebSi
rac Seexeba Rh-genotipebis gavrcelebas filtvis tuberkulozis
wamalrezistentul da sensitiur formebSi, naCvenebia me-14 diagramaze.
0
10
20
30
40
50
60
70
80
90
CC Cc cc EE Ee ee
ფ. ტბ.
დონორი
90
diagr. 14. Rh-Hr sistemis genotipebis gavrcelebis Tavisebureba tuberkulozis rezistentuli da sensitiuri tuberkuloziT daavadebul da donorul populaciebSi
Cc genotipi maRali sixSiriT gvxvdeba (56,63±4,6%) sensitiuri
tuberkulozis SemTxvevebSi, xolo rezistentuli tuberkulozis maCvenebeli
donoruls utoldeba (46.6±5,3%). EE genotipis procentuli maCvenebeli 2.52-
jer maRalia (5,55±2,4%) rezistentul tuberkulozSi, xolo daavadebis orive
formaSi TiTqmis Tanabrad maRalia Ee genotipis maCvenebeli. rac Seexeba CC
genotips, igi mxolod 1.1-jer maRalia daavadebis sensitiur formaSi
donorebTan SedarebiT (diagr. 14).
rezus genotipebidan tuberkulozisadmi mdgradobiT gamoirCeva ee
genotipi, rasac ver vityviT Cc, EE, Ee genotipebze. rezus sistemis es
genotipebi, piriqiT, filtvis tuberkulozur paTologiasTan korelaciiT
xasiaTdebian.
Rh sistemis fenotipebis kvlevisas filtvis tuberkuloziT daavadebul
populaciaSi 0,49%±0,69 sixSiriT dafiqsirda iSviaTi - ccddEe, CCDEe da ccddEE
fenotipi. amaTgan iSviaTi - CCDEe (1,11±1,1) da ccddEE (1,11±1.1) fenotipuri
jgufebi dafiqsirda rezistეntuli tuberkulozisas, xolo ccddEe (0,88±0,03) ki
0
10
20
30
40
50
60
70
80
90
CC Cc cc EE Ee ee
სენსიტ. ტბ.
რეზისტ. ტბ
დონორი
91
- sensitiuri tuberkulozisas. Rh sistemis es fenotipebi donorul
populaciaSi ar gamovlinda.
kvlevis Sedegebze dayrdnobiT, SeiZleba iTqvas, rom CcDEe (19,7±2,7)
fenotipi, romelic 2,46-jer maRali sixSiriT gamovlinda daavadebul
populaciaSi donorulTan (8±2,7) SedarebiT, myarad asocirdeba filtvis
tuberkulozTan (diagr.15).
diagr. 15. Rh-Hr sistemis genotipebis gavrcelebis Tavisebureba tuberkuloziT daavadebul da donorul populaciebSi
rezistentuli tuberkuloziT daavadebul populaciaSi gamovlinda
Ccddee (2,22±1,5), xolo sensitiuri tuberkuloziT daavadebul populaciaSi
mxolod ccDEE (2,65±1,4) fenotipi dafiqsirda (diagr. 16).
-5
0
5
10
15
20
25
30
35
40
45
CcDee ccddee ccDee ccDEe CCDee CcDEe Ccddee ccDEE ccddEe CCDEe ccddEE
ფ.ტბ. %
დონორი%
92
diagr. 16. Rh-Hr sistemis fenotipebis gavrcelebis Tavisebureba tuberkuloziT daavadebul da donorul populaciebSi
miRebuli Sedegebidan gamomdinare, SeiZleba davaskvnaT, rom sensitiuri
tuberkulozi korelirebs CcDEe fenotipTan. misi sixSire 23±3,9%-is tolia,
maSin, roca donorebSi TiTqmis samjer dabalia (8±2.7%). kvlevis SedegebiT,
wamalrezistentuli tuberkulozi korelirebs ccDEe fenotipTan, radgan misi
sixSire 15,55±3,8%-ia, maSin, roca igi sensitiuri formis tuberkuloziT
daavadebul pacientebSi (7,07±2,4) donorebze (10±3%) ufro dabalia.
kvleva Catarda MN jgufuri sistemis mixedviTac, sadac mniSvnelovani
asociaciuri kavSiri gamovlinda filtvis tuberkulozsa da MN sistemis
fenotipur jgufebs Soris.
daavadebul populaciaSi gamoikveTa M(M+N-) fenotipuri jgufis maRali
sixSire (62.5±3,3%), donorebSi ki misi maCvenebeli mniSvnelovnad dabalia
(50,2±5,3). donorul populaciaSi, piriqiT, 1.78-jer maRalia N(M-N+)
fenotipuri jgufis procentuli maCvenebeli (diagr.17).
-5
0
5
10
15
20
25
30
35
40
45
CcDee ccddee ccDee ccDEe CCDee CcDEe Ccddee ccDEE ccddEe CCDEe ccddEE
სენსიტიური%
რეზისტენტ. %
დონორი %
93
diagr. 17. MN sistemis fenotipebis gavrceleba tuberkuloziT daavadebul da janmrTel populaciaSi
rogorc me-18 diagramaze Cans, filtvis tuberkulozis, rogorÝ
wamalrezistentuli (58,8±5,1%), ise sensitiuri (65,4±3.7%) formisas pacientTa
didi umravlesoba M fenotipis matarebelia, sensitiur tuberkulozSi ki
aRniSnuli fenotipuri jgufi 1.11-jer ufro metad gamovlinda, vidre
wamalrezistentulis dros (diagr. 18).
diagr. 18. MN sistemis fenotipebis gavrceleba sensitiuri da rezistentuli tuberkuloziT daavadebul da janmrTel populaciaSi
0
10
20
30
40
50
60
70
80
M N MN
ფ.ტბ.
დონორი
0
10
20
30
40
50
60
70
80
M N MN
სენსიტ. ტბ
რეზისტ. ტბ
დონორი
94
aRsaniSnavia, rom N fenotipis dabali xvedriTi wili gansakuTrebiT
wamalrezistentuli tuberkulozisas dafiqsirda. igi, SesaZloa, aseve
miviCnioT tuberkulozisadmi mdgradobis faqtorad.
aRniSnuli jgufuri sistemis kvlevisas alelebis koncentraciaTa, aseve,
mniSvnelovani sxvaoba gamoikveTa. eqsperimentis Sedegebis Tanaxmad, p(M)
alelis koncentracia SedarebiT maRali (0,75) daavadebul populaciaSi
aRmoCnda, xolo donorebSi - 0,65 iyo. alternatiuli Sedegi dafiqsirda q(N)
alelis kvlevisas. igi mxolod 0,24 sixSiriT gamovlinda daavadebulebSi,
donorebSi ki - 0,35 sixSiriT (diagr.19):
diagr. 19. MN sistemis alelebis gavrceleba tuberkuloziT daavadebul da donorul populaciebSi.
p alelis Tanabrad maRali koncentracia gamovlinda filtvis
tuberkulozis, rogorc wamalrezistentuli, ise sensitiuri pacientebis
SemTxvevaSi da maTi gavrcelebis sixSire, Sesabamisad, 0,75 - 0,76-s Seadgenda,
rac 1,15-1,16-jer maRalia donorebTan SedarebiT. rac Seexeba donorebs, aq
mniSvnelovnad maRali sixSiriT gamovlinda q aleli (0,35) (diagr.20):
0%
50%
100%
p (M)
q (N)
0,75
0,24
0,65
0,35 დონორი
ფ. ტბ
95
diagr. 20. MN sistemis alelebis sixSire tuberkulozis rezistentul da sensitiur formebSi da donorebSi.
miRebuli Sedegebis analizis safuZvelze SeiZleba iTqvas, rom p aleli
da, Sesabamisad, M antigeni sensibiluria tuberkulozis mimarT da maTi
matarebeli individebi miekuTvnebian tuberkuloziT inficirebis maRali
riskis jgufebs, xolo q alelis da, Sesabamisad, N antigenis matarebloba
daavadebis mimarT erTgvar „damcvelobiT“ niSans warmoadgens.
sakvlevi populaciebi Seswavlili iqna Kell sistemis mixedviTac. Kell
fenotipuri jgufebis kvlevisas K+ fenotipuri jgufis gavrcelebis maRali
sixSire (7,3±1,8%) donorebTan (4,2±1,8%) SedarebiT dafiqsirda
wamalrezistentuli tuberkulozis SemTxvevaSi. aseve, donorebTan SedarebiT,
daavadebulebSi 4-jer ufro maRali aRmoCnda p(k) alelis koncentraciac. Kell
sistemis fenotipebis gavrcelebis sixSire da alelTa koncentraciebi
tuberkuloziT daavadebul da janmrTel populaciebSi warmodgenilia 21-e da
22-e diagramebze:
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
სენსიტ.
ტბ
რეზისტ.
ტბ
დონორი
0,23 0,25
0,35
0,76 0,75
0,65
q(N)
p (M)
96
diagr. 21. Kell sistemis fenotipebis gavrcelebis sixSire tuberkuloziT daavadebul da janmrTel populaciebSi.
diagr. 22. Kell sistemis p(K) da q(k) alelTa sixSire tuberkuloziT daavadebul da janmrTel populaciebSi.
Kell sistemis fenotipebi gaanalizebuli iqna tuberkulozis sensitiur da
rezistentul formebSi cal-calke. kvlevam aCvena, rom K+ fenotipi
donorebTan SedarebiT 1,2-jer maRali sixSiriT vlindeba sensitiuri da 2,14-
jer maRali sixSiriT - wamalrezistentuli tuberkuloziT daavadebul
populaciaSi (diagr.23):
0
20
40
60
80
100
120
K+ K-
ფ. ტბ
დონორი
p (K) q(k)
0,08
0,92
0,02
0,97ფ. ტბ დონორი
97
diagr. 23. Kell sistemis fenotipebis gavrcelebis sixSire wamalrezistentuli da sensitiuri tuberkuloziT daavadebul da janmrTel populaciebSi.
Kell sistemis alelebis gavrcelebis sixSiris kvlevis Segdegebis
analiziT miRebuli Sedegebi Semdeg suraTs iZleva: wamalrezistentuli
tuberkulozis SemTxvevaSi q alelis koncentracia 0,1-ia, xolo sensitiuri
tuberkulozisas - 0,05. donorul populaciaSi aRniSnuli aleli mxolod 0,02
sixSiriT aris warmodgenili (diagr. 24):
diagr. 24. Kell sistemis alelebis sixSire wamalrezistentuli da sensitiuri tuberkuloziT daavadebul da janmrTel populaciebSi
p (K)
q(k)0
0,2
0,4
0,6
0,8
1
სენსიტ. ტბ.რეზისტ.ტბ.
დონორი
p (K)
q(k)
98
Kell sistemis analiziT miRebuli Sedegebis miuxedavad, rTulia sarwmuno
daskvnis gakeTeba daavadebasTan misi asociaciuri kavSiris Sesaxeb, vinaidan
Kell dadebiTi fenotipi sxvadasxva eTnikur da maT Soris, qarTul
populaciaSi, Zalian dabali sixSiriTaa gavrcelebuli. miuxedavad amisa,
sakvlev daavadebul jgufSi es antigeni imdenad gansxvavebuli sixSiriT (5-jer
maRali) gvxvdeba, rom didi albaTobiT SeiZleba vivaraudoT filtvis
tubekulozis rezistentul formasTan Kell dadebiTi fenotipisa da p alelis
korelaciis arsebobis Sesaxeb.
III.1.1. sensitiuri da wamalrezistentuli tuberkulozis
asocireba eriTrocituri jgufuri sistemebis (ABO, Rh, MN)
alelebTan saqarTveloSi mcxovreb
azerbaijanul populaciaSi
infeqciuri daavadebebi yovelTvis mniSvnelovan rols TamaSobda
populaciebSi sasargeblo genTa dagrovebasa da genetikuri struqturis
gardaqmnaSi, Sesabamisad, maTi genofondis CamoyalibebaSi. evoluciurad
populaciebis genofondSi dagrovda genTa iseTi aleluri Tu araaleluri
balansi, romelic xelsayreli aRmoCnda im saarsebo garemoSi populaciis
TviTmyofadobisa da homeostazis SesanarCuneblad.
mfd-sadmi memkvidruli midrekileba, maRali variabelobiT xasiaTdeba
da igi pirdapir kavSirSia populaciuri polimorfizmis siZlieresTan.
radganac eTnikuri jgufebi genTa sxvadasxva alels atarebs, romlebic,
aseve, gansxvavebul alelur da araalelur garemocvaSi imyofeba,
gansxvavebulad zemoqmedebs sxvadasxva infeqciuri paTogenis gamovlenis
99
xarisxzec. es gansakuTrebiT exeba imunogenetikur lokusebs. amaze
miuTiTebs qronikuli daavadebebis gamovlenis gansxvavebuli sixSire
populaciebSi, maSinac ki, Tu isini migrirebis gamo msgavs garemoSi an
kidev, erTsa da imave teritoriaze cxovroben an ikaveben sxvadasxva
geografiul areals.
tuberkulozis mimarT msoflios sxvadasxva, maT Soris, erTsa da
imave teritoriaze mcxovreb populaciaSi eriTrocituri jgufuri
antigenebis mimarT vlindeba gansxvavebuli asociaciuri kavSirebi. iaponur
da eskimosur populaciaSi filtvis tuberkulozi asocirdeba B antigenTan,
Sesabamisad, B(III) da AB(IV) fenotipebTan (Saha 1985); indur populaciaSi B(III) da
A(II) feno-jgufTan (Seth et al, 2003); indoeTis teritoriaze mcxovreb andras
regionis populaciaSi B(III) da AB(IV) fenotipur jgufebTan da Rh-- faqtorTan
(Rao & Reddy et al, 2012) da aS.
daavadebebis mimarT populaciebis mgrZnoblobis da misi
ganmsazRvreli gansxvavebuli faqtorebis arsebobis gamo maTi gamovlenis
da Sedarebis mizniT, erT-erT sakvlev jgufad aRebuli iqna saqarTveloSi
mcxovrebi azerbaijanuli populacia. am eTnikuri jgufis warmomadgenlebi
filtvis tuberkuloziT daavadebuli saqarTvelos moqalaqeebis
mniSvnelovan nawils Seadgens.
tuberkulozisa da filtvis daavadebaTa erovnul centris
azerbaijaneli erovnebis pacientiebis kvlevis pirvel etapze eriTrocituri
jgufuri sistemis alelebis gavrcelebis sixSire Seswavlili iqna yvela tipis
tuberkuloziT daavadebul pacientSi. donorebis Sesaxeb monacemebi aRebuli
iqna literaturuli wyarodan.
kvlevis meore etapze sakvlev populaciaSi gamoyofili iqna
tuberkulozis wamalrezistentuli da sensitiuri formiT daavadebuli
pacientebis sakvlevi jgufebi.
filtvis tuberkuloziT daavadebul azerbaijanul populaciaSi
eriTrocituri jgufuri ABO sistemis alelTa kvlevisas janmrTelebTan
SedarebiT daavadebul populaciaSi q alelis mniSnelovnad maRali sixSire
100
dafiqsirda. kerZod, Cvens mier Catarebuli kvlevebiT, daavadebul
populaciaSi misi gavrcelebis sixSire 0.293-s Seadgenda, maSin, roca
literaturuli monacemebis mixedviT, donorul populaciaSi misi
gavrcelebis sixSire mxolod 0,125-ia. aRniSnuli miuTiTebs, rom ABO sistemis
q alelis gavrceleba daavadebul populaciaSi 2.3-jer aRemateba mis
gavrcelebas janmrTel populaciaSi.
SeviswavleT am sistemis r alelis gavrcelebis suraTic. aRmoCnda, rom
igi Tanabari sixSiriT aris warmodgenili orive sakvlev jgufSi, p aleli ki
2,51-jer maRali sixSiriT aris gavrcelebuli donorebSi (diagr.25).
daavadebis wamalrezistentul da sensitiur formebSi q aleli Tanabrad
maRali (0,31-0,29) maCvenebliT dafiqsirda. misi gavrcelebis sixSire
daavadebis formebis Sesabamisad, 2,48 - 2,32-jer maRalia, vidre janmrTel
populaciaSi (diagr.25):
doagr. 25. ABO sistemis r, p, q alelebis gavrceleba filtvis tuberkuloziT daavadebul da janmrTel azerbaijanul populaciaSi
gansakuTrebiT saintereso aRmoCnda P alelis analizis Sedegebi. misi
sixSire donorebSi 3,48 -jer maRali aRmoCnda wamalrezistentul da 1.99-jer
maRali - sensitiuri tuberkulozis SemTxvevebSi dafiqsirebul maCveneblebze
0
0,1
0,2
0,3
0,4
0,5
0,6
rp
q
0,577
0,111
0,293
0,596
0,279
0,125
ფ.ტბ. დონორი
101
(diagr.26). aRniSnuli aleli azerbaijanul populaciaSi SeiZleba ganvixiloT
daavadebis mimaT organizmis mdgradobis ganmapirobebel faqtorebs Soris.
diagr. 26. ABO sistemis r, p, q alelTa koncentracia filtvis sensitiuri da wamalrezistentuli tuberkuloziT daavadebul da janmrTel azerbaijanul populaciaSi
aqedan gamomdinare, SesaZlebelia, dabejiTebiT vTqvaT, rom q aleli
azerbaijanul populaciaSi asocirdeba filtvis tuberkulozis, rogorc
wamalrezistentul, aseve daavadebis sentitiur formasTan, p alelis
matarebloba ki gansazRvravs daavadebis mimarT organizmis mdgradobas da igi
SeiZleba miviCnioT erTgvar damcvel faqtorad.
Rh sistemis alelebis kvlevisas azerbaijanul populaciaSi dafiqsirda
Rh-”d“ alelis 1,23-jer maRali (0,37) sixSire filtvis tuberkuloziT
daavadebulebSi donorebTan (0,30) SedarebiT (diagr.27):
r p q
0,54
0,14
0,29
0,61
0,08
0,31
0,596
0,279
0,125
სენსიტიური რეზისტენტ. დონორი
102
diagr. 27. Rh sistemis alelebis gavrcelebis Tavisebureba filtvis tuberkuloziT daavadebul da janmrTel azerbaijanul populaciaSi
28-e diagramidan Cans, rom miRebuli Sedegebi analogiuria
tuberkulozis wamalrezistentul da sensitiur pacientebSi da misi
gavrcelebis sixSire Seadgens 0.63-s. daavadebis orive formisas RhD”-“
aleli 1.23-jer maRali sixSiriT dafiqsirda janmrTel populaciasTan
SedarebiT.
diagr. 28. Rh D alelis gavrcelebis Tavisebureba rezistentuli da sensitiuri tuberkuloziT daavadebul da janmrTel azerbaijanul populaciaSi
D
d
0,63
0,37
0,699
0,301
ფ.ტბ. დონორი
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
სენსიტიურირეზისტენტ.
დონორი
0,63 0,630,699
0,370,37
0,301 D
d
103
aqedan gamomdinare, SeiZleba, rom tuberkulozisadmi mgrZnobelobis
faqtorad azerbaijanul populaciaSi rezus uaryofiToba miviCnioT.
MN sistemis alelTa kvlevisas gamoikveTa, rom tuberkulozi aRniSnul
populaciaSi korelirebs p (M) alelTan. misi koncentracia daavadebulebSi
0,701-is, donorebSi ki 0,61-is tolia (diagr.29):
diagr. 29. MN sistemis alelebis gavrceleba tuberkuloziT daavadebul da janmrTel
azerbaijanul populaciaSi
rac Seexeba MN sistemis q alels, igi donorul populaciaSi
warmodgenilia SedarebiT maRali sixSiriT (0,39) daavadebulebTan
SedarebiT (0,29) (diagr.29).
msgavsi suraTi gamoikveTa filtvis tuberkulozis orive formis
SemTxevaSi. P(M) alelis gavrcelebis sixSire Tanabrad maRali maCvenebliT
dafiqsirda (diagr.30):
q(N) p (M)
0,29
0,701
0,39
0,61
ფ.ტბ. დონორი
104
diagr. 30. MN sistemis alelebis gavrceleba senstiuri da wamalrezistentuli tuberkuloziT daavadebul da janmrTel azrbaijanel populaciaSi
daavadebis rogorc sensitiuri, ise wamalrezistentuli formis
SemTxvevaSi msgavsi Sedegi gamoikveTa. orive formis tuberkulozi
azerbaijanul populaciaSi Tanabari siZlieriT korelirebs p alelTan da
misi matarebeli individebi SeiZleba CaiTvalos tuberkuloziT inficirebis
risk-jgufebad. rac Seexeba q alels, didi albaTobiTaa SesaZlebeli, igi
ganxilul iqnes tuberkulozis mimarT organizmis mdgradobis erT-erT
faqtorad.
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
სენსიტ. ტბრეზისტ. ტბ
დონორი
0,310,27
0,39
0,68 0,72
0,61
q(N)
p (M)
105
III.1.2. eriTrocituri ABO (r,p,q), Rh-Hr (RhD+,RhD-) daMN (p,q)
jgufuri sistemis alelTa gavrcelebis SedarebiTi analizi tuberkuloziT
daavadebul qarTul da azerbaijanul populaciebSi
cnobilia, rom qarTuli da azerbaijanuli populaciebi, kavkasiis
mkvidri, SedarebiT msgavs geografiul sivrceSi mcxovrebi eTnikuri
jgufebia. wlebis manZilze gadamrCevi faqtorebis zemoqmedebis Sedegad,
isini konkretul saarsebo garemos Seegua maTi genetikuri struqturis
cvlilebis safuZvelze. ramdenadac kavkasiis regioni paTogenebis
gavrcelebisa Tu daavadebaTa gamomwvevi faqtorebis gamo sakmaod
gansxvavebulia, Sesabamisad, aq mcxovreb populaciebs sxvadasxva tipis
daavadebisadmi mgrZnobelobis Tu mdgradobis gansxvavebuli unari
CamouyalibdaT.
iseve, rogorc bevri sxva genetikuri niSani, eriTrocituri jgufuri
antigenebiT determinirebuli sisxlis fenotipuri jgufebis sixSirec
araTanabrad aris ganawilebuli azerbaijanul da qarTul populaciebSi.
Tumca, rogorc qarTul, aseve azerbaijanul populaciaSic dominirebs
sisxlis O(I) fenotipuri jgufi.
populaciur-genetikuri kvlevebisTvis alelebis Seswavla ufro
sarwmuno informacias iZleva, amitom kvlevas eriTrocituri ABO jgufuri
sistemis - (r (0), p (A) da q (B), rezus sistemis - RhD“+“ da RhD“-„ da MN sistemis -
p (M) da q (N) alelebis doneze vawarmoebdiT.
kvlevis Sedegad gamovlinda garkveuli Tavisebureba ABO da Rh-Hr
sistemis alelTa gavrcelebis mixedviT, qarTul da azerbaijanul rogorc
donorul, ise daavadebul populaciebSi.
aRmoCnda, rom qarTul da azerbaijanul populaciebSi ABO sistemis r, p
da q alelebis sixSires Soris Tanafardoba gansxvavebulia. qarTul
populaciaSi r alelis koncentracia 0,69-is tolia, azerbaijanulSi 0,596-s
Seadgens, anu qarTul populaciaSi misi gavrcelebis sixSire 1.15-jer maRalia,
106
vidre azerbaijanulSi. Tumca, r aleli orive populaciaSi gavrcelebis mxriv
pirvel adgils ikavebs, momdevno adgilze p aleli dgas, xolo yvelaze mcire
sixSiriT, rogorc qarTul, ise azerbaijanul populaciaSi q alelia warmod-
genili. maTi gavrcelebis ricxobriv maCveneblebs Semdegi saxe aqvs:
- P alelis koncentracia azerbaijanul populaciaSi 0,279-is, xolo
qarTulSi - 0,09-is tolia, anu azerbaijanul populaciaSi igi 3.1-jer
maRali koncentraciiTaa warmodgenili;
- q alelis sixSire azerbaijanul populaciaSi 0,125-s Seadgens, xolo
qarTul populaciaSi 0,23-s utoldeba, anu 1.92-jer maRali sixSiriT
gavrcelebuli qarTul populaciaSi.
filtvis tuberkulozTan ABO sistemis r, p da q alelebis korelaciis
Sesaswavlad Catarebuli kvlevebis safuZvelze gamovlinda, rom orive
eTnikuri jgufi gansxvavebulad avlens korelacias filtvis tuberkulozTan.
aRmoCnda, rom filtvis tuberkulozTan qarTul populaciaSi r aleli
korelirebs, sadac igi 1.08-jer maRali sixSiriTaa warmodgenili donorul
populaciasTan SedarebiT, maSin, roca r aleli azerbaijanul populaciaSi
donorebSia ufro maRali (0,596) koncentraciiT warmodgenili, vidre
daavadebul populaciaSi (0,557).
saintereso sxvaoba dafiqsirda, aseve, p da q alelebis kvlevisas.
filtvis tuberkuloziT daavadebul qarTul populaciaSi p aleli Tanabrad
aris ganawilebuli daavadebul da donorul populaciaSi, xolo daavadebul
azerbaijanul populaciaSi aRniSnuli alelis matarebloba aSkarad
ganapirobebs organizmis mdgradobas filtvis tuberkulozis mimarT. amaze
metyvelebs is faqti, rom p aleli daavadebulTan SedarebiT 2.5-jer maRali
koncentraciiTaa warmodgenili janmrTel azerbaijanul populaciaSi (0,279)
(cxr. 4).
tuberkulozTan q aleli qarTul populaciaSi aranair korelacias ar
avlens, azerbaijanul populaciaSi ki aSkarad korelirebs daavadebasTan. am
107
daskvnis safuZvels is faqti iZleva, rom daavadebul azerbaijanul
populaciaSi q aleli 2,34-jer maRali sixSiriTaa warmodgenili donorebTan
SedarebiT.
aqedan gamomdinare, SeiZleba davaskvnaT, rom filtvis tuberkulozi
qarTul populaciaSi asocirdeba ABO sistemis r alelTan, azerbaijanul
populaciaSi ki - q alelTan.
rezus sistemis Rh-D da Rh“d„ alelebis kvlevisas eTnikur jgufebSi
dafiqsirda alternatiuli Sedegebi. filtvis tuberkulozi qarTul
populaciaSi korelirebs Rh-D alelTan, xolo azerbaijanul populaciaSi -
Rh-“d„ alelTan.
Seswavlili iqna MN sistemis alelebis sixSire orive eTnikuri jgufis
filtvis tuberkuloziT daavadebul pacientebSi. kvlevis Sedegad aRmoCnda,
rom aRniSnuli sistemis alelebi orive eTnikur jgufSi msgavs korelacias
avlenen daavadebasTan. kerZod, p(M) alelis kvlevisas filtvis tuberkuloziT
daavadebul qarTul populaciaSi misi gavrcelebis sixSire 0,73-s Seadgens
anu 1.12-jer maRalia donorul populaciasTan mimarTebaSi. azerbaijanul
populaciaSi ki igive aleli 1.14 -jer maRali iyo daavadebul pacientebSi.
q(N) aleli orive sakvlevi populaciisTvis, savaraudod, tuberkulozi-
sadmi mdgradobis ganmapirobebel alels SeiZleba mivakuTvnoT. misi
koncentracia Tanabrad - 1.34-jer naklebia daavadebulebSi, rogorc qarTuli,
aseve azerbaijanuli populaciisTvis, xolo janmrTel populaciaSi
sarwmunod maRali koncentraciiT (0.29) - qarTul da 0.39 - azerbaijanul
populaciaSi.
108
genetikuri sakvlevi jgufebi
markerebi alelebi
f. tb f.tb. donori donori
qarT. pop. azer. pop. qarT. pop. azer.pop.
ABO r (0) 0.739 0.557 0.68 0.596
p (A) 0,85 0.111 0.09 0.279
q (B) 0,185 0.293 0.23 0.125
Rh-Hr RhD+ 0.57 0.63 0.54 0.699
RhD- 0.25 0.37 0.43 0.301
M N
M(P) 0.73 0.701 0.65 0.61
N(q) 0.26 0.29 0.35 0.39
n =203 n=92 n=485
cxr. 4. ABO, Rh da NM sistemis alelebis gavrcelebis Tavieburebani qarTul da azerbaijanul donorebSi da filtvis tuberkuloziT daavadebul populaciebSi.
filtvis tuberkulozTan ABO da Rh eriTrocituri jgufuri sistemebis
alelTa gansxvavebuli korelaciuri kavSiri da MN sistemis alelTa msgavsi
korelaciis gamovlena daavadebasTan qarTul da azerbaijanul
populaciaSi, SesaZlebelia, aixsnas populaciur doneze mudmivad moqmedi
elementaruli evoluciuri faqtorebis Sedegad (genebis dreifi, mutaciuri
procesi, genuri nakadebi, izolacia, bunebrivi gadarCeva da a.S.), ris
safuZvelzec zemoT ganxiluli antigenuri determinantebis mixedviT
Camoyalibda balansuri polimorfizmi. eriTrocituri jgufuri sistemebis
ganmapirobebel da mis garemocvaSi myof sxva imunogenetikur lokusebs Soris
damyarda garkveuli wonasworuli balansi, ramac ganapiroba ABO, Rh da MN
sistemis alelTa specifikuri asociaciuri kavSirebis Camoyalibeba filtvis
tuberkulozis mimarT qarTul da azerbaijanul populaciebSi.
109
III.2. IgM, IgG da IgA imunoglobulinebis done filtvis
tuberkuloziT daavadebulebSi
bolo aTwleulebSi imunologiuri kvlevis teqnikis daxvewam
ganapiroba mzardi interesi antituberkulinuri imunuri pasuxis ukeT
gasagebad da am mimarTulebiT mravali mecnieruli kvleva iqna Catarebuli
msoflios sxvadasxva populaciaSi.
Mycobacterium tuberculosis-iT organizmis inficirebis Semdeg mniSvnelovan
rols asrulebs ujreduli (specifikuri) imunuri pasuxi. ujredSida
paTogenis kontrols da mis ganadgurebas T-ujredebis efeqtoruli meqanizmebi
uzrunvelyofs (Bothamley et al., 1995). adre fiqrobdnen, rom humoruli imunuri
pasuxis damcvelobiTi roli minimaluri iyo tuberkulozuri infeqciisas.
magram mecnierTa interesis gaZlierebam da kvlevebis speqtris gafarToebam
aCvena, rom antigeniT gaaqtivebuli B- ujredebi da maT mier sinTezirebuli
antisxeulebi antituberkulozuri imunitetis mniSvnelovani Semadgeneli
nawilia. antigen-antisxeulis reaqciebi aCqarebs dendrituli ujredebis,
makrofagebis da antigen- specifikuri T-limfocitebis lokalur akumulacias
dazianebul kerebSi da zrdis mikobaqteriis mimarT ujredul imunur pasuxs
(Dannenberg, 2006; Palomino et al., 2007). IgA-s mniSvnelovani roli akisria
mikobaqteriisgan organizmis dacvaSi. igi lorwovani garsebis mTavari
imunoglobulinia (Julian et al.,2000; de Larrea et al.,2006). garda IgA-sa, IgG-c
mniSvnelovan rols asrulebs tuberkulozuri infeqciis marTvis procesSi.
mikobaqteriuli antigeniT aqtivirebuli T-ujredebi urTierTqmedeben
B-ujredebTan, romlebic, Tavis mxriv, jer IgM-s asinTezeben, xolo
mogvianebiT, infeqciuri procesidan aRdgenis periodSi xdeba IgG-s sinTezi,
romelic specifikurad anadgurebs SeWril mikroorganizms. igive
mikroorganizmis xelmeored SeiWrisas maspinZel organizmSi B ujredebi
110
dauyovnebliv warmoqmnian specifikur IgG antisxeulebs mikrobis
gasanadgureblad (Jain et al.,1984, Palomino et al.,2007).
sxvadasxva paTogenis mimarT organizmis mier producirebuli
antisxeulebi sakmaod Zlier markerebs warmoadgenen infeqciuri daavadebis
diagnostikis TvalsazrisiT da maTi gamovlena sakmaod iafi da martivia,
amitom serologiurma diagnostikam kargad moikida fexi (Silva et al., 2003).
mikobaqteriis winaaRmdeg ganviTarebuli humoruli imunuri pasuxi SeiZleba
gamoyenebul iqnes tuberkulozis adreuli serodiagnostikis saqmeSic
(Bothamley, 1995; Lenka, 2003; Demkow et al., 2005; Demkow et al., 2006; Senol, 2006; Liu et
al., 2007; Araujo et al., 2008; Bezerra et al., 2009). tuberkulozis SemTxvevaSi
serologiuri testebis specifikuroba mas Semdeg gaumjobesda, rac
gamovlenili iqna mikobaqteriuli kompleqsis maRal-specifikuri da
rekombinantuli antigenebi (Demkow et al., 2002).
mikobaqteriis mravalferovani antigenuri determinantebis
(polipeptidebi, romlebic Trgunaven makrofagebis funqcias da iwveven
ujredul imunur pasuxs: molekuluri masis cilovani antigenebi 71, 65, 38, 36,
23, 19, 16, 14 da 12kd, romelTagan 36kd da 16kd dominanturi antigenebia,
polisaqaridebi - II-arabinomanani (LAM), romelic Trgunavs T-ujredebis
proliferacias) winaaRmdeg organizmi gamoimuSavebs sxvadasxva klasis (IgA,
IgG, IgM) specifikur antisxeulebs, romelTa aRmoCena SeiZleba pacientis
SratSi imunofermentuli (ELISA) meTodiT (Tomoka et al., 1990; Demkow et al., 2002;
Beck et al., 2005).
antituberkulozuri humoruli imunuri pasuxisas, aqtiuri
tuberkulozis dros gamomuSavebuli antisxeulebi ZiriTadad IgM da IgG
klasisaa. aRniSnuli antisxeulebi avlenen maRal specifikurobas da
mgrZnobelobas mikobaqteriis antigenuri determinantebis mimarT (Julian et al.,
2004; Bam & Karn., 2009). mkvlevarTa meore jgufis mier Catarebul gamokvlevebSi
111
naCvenebia, rom mikobaqteriuli infeqciisas mniSvnelovania, aseve, IgA (Julian et
al., 2004).
naklebadaa Seswavlili imunuri sistemis mdgomareoba daavadebis
sxvadasxva klinikuri formis dros. cnobilia, rom daavadebis stadiebis
mixedviT imunoglobulinebis done cvalebadobs. daavadebis meore stadiaze
mniSvnelovnad izrdeba IgG, IgA da IgM done pirvel stadiasTan SedarebiT,
mesame stadiaze - IgG da IgA done. daavadebis klinikur formebSi cnobilia, rom
IgG-is done maRalia tuberkulozis eqsudaciuri da kavernozuli
dazianebebisas fibro-produqciul da fibrokavernozul formasTan SedarebiT
(Jain et al.,1984). Cvens mier Seswavlili iqna organizmis humoruli imunuri
pasuxi daavadebis kerovani, fibro-kavernozuli da rRvevis fazaSi myofi
infiltraciuli formis dros. amasTanave, radganac tuberkulozis mZime
klinikuri formebi xSir SemTxvevaSi asocirdeba baqteriis rezistentobis
CamoyalibebasTan, swored amitom, igive kvleva ganvaxorcieleT tuberkulozis
rezistentuli da wamlis mimarT sensitiur formebSi. amasTanave,
mikobaqteriuli infeqciisas antisxeulebis done daavadebis
wamalrezistentul formebSi TiTqmis Seuswavlelia.
gamokvleuli iqna sami klasis imunoglobulinebis - IgG, IgM da IgA done
filtvis tuberkulozis sensitiuri da rezistentuli formisas da aseve,
daavadebis kerovani, fibro–kavernozuli da rRvevis fazaSi myofi
infiltraciuli formebis dros. saerTo imunoglobulinebis donis
Seswavlis garda, kvlevas vatarebdiT specifikuri antituberkulinuri
imunoglobulinebis jamuri (Ig G+M+A) donis Seswavlis mizniTac.
gamokvleuli 30 pacientidan (asakobrivi jgufi 16–73 wlamde), 15
iyo filtvis tuberkulozis kerovani formis mqone, xolo 15 -
infiltraciuli tuberkuloziT rRvevis fazaSi. sakontrolo masalad
aRebuli iqna imave asakobrivi jgufis 30 janmrTeli moxalise. aseve,
gamokvleuli iqna antisxeulebis titri wamalrezistentuli da wamalTa
112
mimarT sensitiuri tuberkuloziT daavadebul pacientebSi (30– sensitiuri, 30–
wamalrezistentuli formiT). sensitiuri formis mqone 30 pacientidan xuTi,
xolo rezistentuli 30 pacientidan rva iyo mdedrobiTi sqesis.
Catarebuli eqsperimentis Sedegad gamovlinda, rom filtvis tuberku-
lozisas, Cveulebriv, IgG klasis specifikuri antisxeulebi Warbobs, IgM
antisxeulebi, ufro metad, daavadebis sawyis stadiaze Cndebian, xolo IgA
gvxvdeba ufro iSviaTad, amitom saWirod miviCnieT jamuri antisxeulebis
gansazRvra.
mikobaqteriis sawinaaRmdego specifikuri jamuri antisxeulebis
Seswavlisas fibro-kavernozuli, infiltraciuli rRvevis fazaSi myofi da
kerovani tuberkuloziT daavadebul pacientebSi jamuri antisxeulebis (IgG +
M + A) done mniSvnelovnad maRali aRmoCnda fibro-kavernozuli (saSualo
maCvenebelia 0,695±0.01) da rRvevis stadiaSi myofi infiltraciuli (saSualo
maCvenebeli - 0,687±0.01) tuberkulozis mqone pacientebSi, sakontrolo,
janmrTel populaciasTan SedarebiT. miRebuli monacemebis Tanaxmad
aRniSnuli maCveneblis saSualo sidide 0,257 iyo, sarwmunoobis maCvenebeli
Seadgenda P<0,05. jamuri imunoglobulinebi mniSvnelovnad maRali titriT
dafiqsirda kerovani formis tuberkuloziT daavadebul pacientebSi, sadac
igi Seadgenda 0,489±0.01, xolo P<0,001 (diagr. 31).
113
sakontrolo jgufi
kerovani infiltr.
rRv. faza fibr/kav.
0.257±0.03 0.489±0.01 0.687±0.01 0.695±0.01
diagr. 31. jamuri (IgG, IgA, IgM) antisxeulebis saSualo optikuri simkvrive tuberkulozis sxvadasxva stadiaze (1-sakontrolo jgufi, 2- kerovani, 3- infiltraciuli tb rRvevis fazaSi,
4-fibro-kavernozuli, opt. – 405 nm)
rogorc gamokvlevam gviCvena, tuberkulozuri daavadebis sxvadasxva
klinikuri formisas specifikuri imunoglobulinebis done gansxvavebulia.
zogierTi avtori amtkicebs, rom daavadebis garTulebuli mimdinareobisas,
romelsac Tan axlavs filtvis qsovilis destruqciuli cvlilebebi,
organizmis imunuri sistemis humoruli rgoli reagirebs IgE-is sinTezis
gaZlierebiT IgG-is sinTezis daTrgunvis fonze, xolo IgM da IgA-s
koncentracia praktikulad ar icvleba (Jain et al., 1984; Rohini et al., 2012). Tumca,
Cvens SemTxvevaSi daavadebis formis simZimesTan erTad specifikuri jamuri
antisxeulebis done matulobs. yvelaze maRali maCvenebeli dafiqsirda fibro–
kavernozuli tuberkulozis dros, Tumca, es maCvenebeli didad ar gansxvavdeba
infiltraciuli rRvevis fazaSi myofi pacientebis maCveneblisagan. rogorc
Cans, daavadebis fazis sirTulesTan erTad adgili aqvs imunostimulacias,
rac antisxeulebis sinTezis matebaSi gamoixateba. savaraudod, es maCvenebebli
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
46
0ნმ
საკონტ.ჯგ
კეროვ.ტბ.
ინფ. ტბ
რღვ.ფ.
ფიბრ/კავ.
114
SeiZleba dagvexmaros daavadebis fazebis diferencirebul diagnostikaSi,
rogorc damatebiTi informacia.
radgan daavadebis fazebTan mimarTebaSi adgili hqonda
imunoglobulinebis koncentraciis cvlilebebs, mizanSewonilad CavTvaleT,
Segveswavla, axdenda Tu ara gavlenas mkurnaloba antibaqteriul humorul
imunitetze. aRmoCnda, rom specifikur antisxeulTa titri xangrZlivad
namkurnalev pacientebSi pirvelad pacientebTan (axal dawyebuli mkurnalobiT
an aranamkurnalevi) SedarebiT ufro maRali iyo (diagr. 32), rac sruliad
adekvaturia, radgan xangrZlivi mkurnalobis qveS, umetesad,
wamalrezistentuli pacientebi imyofebebodnen, romlebSic baqteriis
koncentacia maRali unda iyos da imunuri sistema, Sesabamisad, antisxeulebis
matebiT pasuxobs.
savaraudod, antituberkulinuri jamuri antisxeulebis koncentraciis
Seswavla efeqturi iqneba mkurnalobis monitoringis TvalsazrisiTac.
diagr. 32. specifikuri jamuri ( IgG, IgA, IgM) antisxeulebis done donorebSi, namkurnalev da aranamkurnalev pacientebSi
literaturul monacemebSi aris informacia imis Sesaxeb, rom
tuberkuloziT avadobisas mniSvnelovnad matulobs specifikuri
antituberkulozuri IgG da mis gansazRvras aqvs didi mniSvneloba daavadebis
0
0,1
0,2
0,3
0,4
0,5
0,6
donori xanm. xang.
%
115
prognozirebis TvalsazrisiT. IgG-Tan erTad IgM-s gansazRvris SemTxvevaSi
bevrad izrdeba specifikuroba mikobaqteriuli antigenebis mimarT da,
Sesabamisad, misi prognozuli mniSvneloba aRwevs 88,5%-s (Lenka, 2003; Bam &
Karn 2009). aRniSnulidan gamomdinare, jamuri antisxeulebis donis gansazRvra
ufro efeqturia am TvalsazrisiT, vidre TiToeulisa cal-calke.
specifikuri antituberkulinuri imunoglobulinebis jamuri
koncentracia, rogorc Cans, damokidebulia daavadebis formasa da fazaze,
lokalizaciaze da organizmSi daavadebis gavrcelebaze. xSirad, daavadebis
gamwvavebisas aRiniSneba antisxeulebis koncentraciis talRiseburi cvlileba
(Jain et al., 1984). saerTo jamSi, antisxeuluri pasuxis suraTi tuberkulozis
dros Zalian individualuri da rTulia. amitom saWirod CavTvaleT,
zogadad humoruli imunuri pasuxis dadgenis mizniT gamogvekvlia filtvis
tuberkuloziT daavadebulebSi saerTo imunoglobulinebis, kerZod, IgG,
IgM da IgA-s koncentraciac.
filtvis tuberkuloziT daavadebuli pacientebis sisxlis SratSi
imunoglobulinebis (IgA, IgG, IgM) saerTo donis gansazRvris mizniT
Catarebuli kvlevis Sedegad gamovlinda, rom samive imunoglobulinis - IgA, IgG
da IgM done filtvis tuberkuloziT daavadebul pacientebSi maRali
koncentraciiT dafiqsirda. gansakuTrebiT maRali iyo IgG-s (1757,432) done,
Semdeg - IgM (437,8162) da IgA-isa (363,1182), sakontrolo jgufTan (IgA - 235±233
mg/dl, IgG - 1150±636 mg/dl, IgM - 135±134 mg/dl.) mimarTebaSi (diagr. 33):
116
diagr. 33. imunoglobulinebis IgG, IgA da IgM saerTo done (mg/dl) filtvis tuberkuloziT daavadebul pacientebSi da sakontrolo jgufSi
filtvis tuberkulozis wamalrezistentul da sensitiur pacientebSi
imunoglobulinebis saerTo done Semdeg suraTs iZleoda: sensitiur formebSi
- IgA - 362,16±214,35 mg/dl, IgG -1878,96±1093,88 mg/dl, IgM - 426,84±845,63 mg/dl,
xolo wamalrezistentul formebSi - IgA - 381,49±225,71 mg/dl, IgG -
1696,91±1049,37 mg/dl, IgM - 467,70±948,56 mg/dl koncentraciiT dafiqsirda
(diagr.34):
diagr. 34. imunoglobulinebis IgG, IgA da IgM saerTo done (mg/dl) tuberkulozis wamal- sensitiur da wamal-rezistentul formebSi da sakontrolo jgufSi
363,1182
1757,432
437,8163
235
1150
135
0
200
400
600
800
1000
1200
1400
1600
1800
2000
IgA IgG IgM
ტბ.
კონტრ.
362
1878
426381
1696
467
0
200
400
600
800
1000
1200
1400
1600
1800
2000
IgA IgG IgM
საკონტრ.ჯგ.
სენსტ.
რეზისტ.
117
IgG da IgM-is done IgA-Tan SedarebiT, tuberkuloziT daavadebuli
pacientebis SratSi (P<0.001) sakontrolo jgufTan (P<0.05) SedarebiT maRali
koncentraciiT dafiqsirda. IgA umniSvnelod maRali koncentraciiT iyo
momatebuli filtvis tuberkulozis, rogorc wamalrezistentuli, ise sensi-
tiuri formiT daavadebulebSi (P<0.01) (diagr. 34).
IgG daavadebis sensitiur formaSi 1.107-jer maRali iyo, vidre
wamalrezistentul tuberkulozSi. IgM da IgA-s mixedviT mniSvnelovani
sxvaoba ar gamovlenila, orive klasis imunoglobulini sakontrolo jgufTan
SedarebiT, Tanabrad maRali koncentraciiT iyo warmodgenili, rogorc
sensitiur, ise wamalrezistentuli tuberkulozis mqone pacientebSi (diagr.
34).
imunoglobulinebis done filtvis tuberkuloziT daavadebul
pacientebSi Seswavlili iqna sqesis mixedviTac. sensitiuri tuberkuloziT
daavadebul mdedrobiTi sqesis individebSi Sratis imunoglobulinebis done
Semdeg suraTs iZleva: IgA - 396,18±160mg/dl, IgG - 1865,0±915mg/dl da IgM -
295,5±208mg/dl; mamrobiTi sqesis pacientebSi ki – IgA - 348±214mg/dl, IgG -
1875±1146 mg/dl, IgM - 436±883mg/dl. aRniSnuli monacemi samive
imunoglobulinis, gansakuTrebiT ki IgG-s SemTxvevaSi, maRali iyo
sakontrolo jgufTan SedarebiT, sadac imunoglobulinebis koncentracias
Semdegi saxe aqvs - IgA-s done 235±233mg/dl-ia (P<0.05), IgG - 1150±636mg.dl
(P<0.001) da IgM - 135±134mg/dl (P<0.05) (diagr. 35).
118
diagr. 35. imunoglobulinebis saerTo done (mg/dl) sensitiuri tuberkulozis mqone qalebsa da mamakacebSi sakontrolo jgufTan SedarebiT
daavadebis wamalrezistentul formebSic msgavsi monacemebi
dafiqsirda. filtvis tuberkuloziT daavadebul mdedrobiT da mamrobiT
pacientebSi imunoglobulinebis maCveneblebs Semdegi saxe aqvs - IgA qalebSi-
358±183mg/dl, mamakacebSi-386,68±235mg/dl; IgG - qalebSi-1686±1048mg/dl,
mamakacebSi 1624.95±1158 mg/dl; IgM -qalebSi - 308±166 mg/dl, mamakacebSi-
521.93±893 mg/dl. (diagr. 36).
diagr. 36. imunoglobulinebis saerTo done (mg/dl) mdedrobiTi da mamrobiTi sqesis wamalrezistentuli tuberkulozis mqone pacientebSi da sakontrolo jgufSi
235
1150
135
396
1865
296384
1875
436
0
200
400
600
800
1000
1200
1400
1600
1800
2000
IgA IgG IgM
საკონტრ.გჯუფი
ქალები
მამაკაცები
235
1150
135
358
1686
308368
1626
521
0
200
400
600
800
1000
1200
1400
1600
1800
IgA IgG IgM
საკონტრ.ჯგ.
ქალები
მამაკაცები
119
literaturuli monacemebiT, janmrTel populaciaSi IgM da IgG-s
koncerntraciebSi sqesis mixedviT arsebiTi gansxvaveba ar fiqsirdeba. Cvens
SemTxvevaSi tuberkulozis, rogorc sensitiuri ise wamalrezistentuli
formiT daavadebulebSi IgM-is done mamrobiTi sqesis pacientebSi
mniSvnelovnad maRali (sensitiuri tb - 436±883mg/dl wamalrezistentuli tb.-
521.93±893mg/dl) iyo, vidre mdedrobiTi sqesis pacientebis sisxlis SratSi
(sensitiuri tb. - 295,5±208mg/, wamalrezistentuli tb. - 521.93±893mg/dl) da
sakontrolo jgufSi (135mg/dl) (P<0.01) (diagr.36). aRniSnuli SesaZloa
gamowveuli iyos cxovrebis maTi wesidan gamomdinare. analogiuri Sedegebi
fiqsirdeba literaturul wyaroebSic (alarchon-Segovia & Fishbein, 1971; Maddison
et al., 1975)
rogorc kvlevis Sedegebma gviCvena, antisxeulebis maRali titrs
ganpirobebda IgG-s koncentraciis sagrZnobi mateba. aRniSnuli
imunoglobulinis done daavadebis, rogorc sensitiuri, ise
wamalrezistentuli formisas sagrZnoblad maRalia sakontrolo jgufTan
SedarebiT (P<0.001). es exeba, rogorc mdedrobiTi, ise mamrobiTi sqesis
pacientebs (diagr.37).
sensitiuri tuberkulozis SemTxvevaSi IgG-s koncentracia orTave sqesis
warmomadgenlebSi Tanabrad maRali maCvenebliT dafiqsirda (diagr.36), xolo
daavadebis rezistentul formaSi igi 1.05-jer maRali koncentraciiT -
qalebSi, vidre mamakacebSi (diagr.37).
120
diagr. 37. imunoglobulin IgG –s (mg/dl) done mdedrobiTi da mamrobiTi sqesis sensitiur da wamalrezistentul pacientebSi da sakontrolo jgufSi
Catarebuli kvlevebidan gamomdinare, filtvis tuberkuloziT
daavadebul pacientebSi specifikuri anti-tuberkulozuri antisxeulebis
gamovlena mniSvnelovania tuberkulozis sxvadasxva klinikur formaSi.
gansakuTrebiT mniSvnelovania rRvevis stadiaSi myofi infiltraciuli
tuberkulozisas da daavadebis fibrozul/kavernozuli formisas, radgan
aRniSnuli monacemi SeiZleba gamoyenebuli iqnes, rogorc damatebiTi
diagnostikuri meTodi. radgan, baqterioskopuli gamokvlevebi xSirad ar
iZleva zusti diagnozis dasmis saSualebas da bavSvebSi TiTqmis ar gamoiyeneba
masalis mopovebis sirTulis gamo, xolo kulturis meTodi xangrZliv dros
moiTxovs. sakmaod zusti imunofermentuli analizis (ELISA) meTodiT
pacientis SratSi arsebuli specifikuri antisxeulebis titris gansazRvra
daavadebis adreul stadiaze daavadebis adreuli diagnostirebis saSualebas
iZleva (Bam& Karn 2009).
imunoglobulinebis saerTo donis gansazRvris Sedegad Cvens mier
miRebuli Sedegebi emTxveva samecniero literaturaSi arsebul monacemebs,
romlis Tanaxmad specifikur IgG antisxeuls aqvs maRali specifikuroba da
mgrZnobeloba mikobaqteriuli antigenebis mimarT. Tu IgG-Tan erTad IgM-is
donis gansazRvra moxdeba, mniSvnelovnad izrdeba diagnostirebis
1865 1875
1150
1686 1626
0
200
400
600
800
1000
1200
1400
1600
1800
2000
კონტრ. ქალები მამაკაცები
სენს. ტბ.
რეზ.ტბ.
121
specifikurobis xarisxi, rasac tuberkulozis diagnostirebisTvis didi
mniSvneloba aqvs (Bam & Karn, 2009).
rac Seexeba humorul imunur pasuxs (imunoglobulinebis saerTo
koncentracia), filtvis tuberkulozis sensitiuri da rezistentuli
formebisas mniSvnelovan sxvaobas ar iZleva da organizmi daavadebis orive
formis dros aviTarebs msgavs imunur pasuxs, rac gamoixateba IgG-s donis
mniSvnelovan matebaSi.
Cvens mier miRebuli Sedegebi, am mxriv, emTxveva sxva avtorebis monacemebs
(Fabio et al., 1994; Lenka et al., 2003), romlebic aRniSnaven, rom tuberkulozuri
paTologiisas organizmSi mniSvnelovnad izrdeba IgG antisxeulebis done.
122
III.3. SLC11A1 genis D543N lokusis polimorfizmis
Seswavla filtvis tuberkulozis wamalrezistentuli da
sensitiuri formebiT daavadebul pacientebSi
tuberkulozis mimarT organizmis winaswarganpirobebulobaSi monawile
kandidat genebs (TLR (Medzhitov, 2001; Krutzik et al, 2001), MHC (HLA) (Palomino et.al
2007; Taype et.al. 2010), IFN-γ Hill 2006; Taype et al., 2006), TGF (Moore et al., 2001; Niimi et
al., 2002; Henao et al., 2006; Oral et al., 2006; Mak et al., 2007), VDR (Prithvi R. et.al. 2011)
Soris yvelaze metad bunebriv mdgradobasTan asocirebuli geni SLC11A1-ia
Seswavlili. mis mier kodirebuli makrofaguli cila 1 (NRAMP1) monawileobs
rkinis ionebis membranul cvlaSi, ris Sedegadac xdeba makrofagebis aqtivacia
da maspinZlis antimikrobuli radikalebis generalizeba, rasac mniSvnelovani
damcvelobiTi funqcia aqvs mikobaqteriis winaaRmdeg ganviTarebul imunur
pasuxSi (Blackwell et al, 2000, 2003; Goswami et al, 2001).
saqarTveloSi filtvis tuberkuloziT daavadebuli pacientebSi,
romlebic Cveni kvlevis obieqts warmoadgenda, daavadebis winaswar-
ganpirobebulobaSi Tu mis klinikur ganviTarebaSi monawile kandidati genebi
Seuswavlelia. qveyanaSi wamalrezistentuli tuberkulozis maRali
prevalentobis da mis zogierT eTnoteritoriul jgufSi [Sida qarTlis, qvemo
qarTlis, kaxeTis, aWaris, imereTis da samegrelos regionebi (USAID 2007)],
daavadebis maRali gavrcelebis gamo sakiTxi gansakuTrebiT aqtualuria.
Cvens mier Seswavlili iqna SLC11A1 genis D543N lokusi misi
polimorfuli variaciebis, filtvis tuberkulozis wamalrezistentul
formebTan SesaZlo asociaciuri kavSiris gamovlenis mizniT.
SLC11A1 moTavsebulia me-2 qromosomis grZeli mxris 36.1 lokusSi (2q36.1)
(sur. 13):
123
sur. 13. SLC11A1 genis lokusi me-2 qromosomaSi.
SLC11A1 genis oTx sxvadasxva lokuSi (sqema.1) gamovlenili - 5´(GT)n
(mikrosatelituri ubani G/T cvalebadi raodenobis ganmeorebadi
Tanmimdevrobebi (n) SLC11A1 5’-dan); INT4 (erTnukleotidiani cvlileba me-4
intronSi 4: 469+14G/C-Si); D543N (me-15 egzonis 543 kodonSi momxdari
cvlilebiT, romelic iwvevs asparaginis mJavis aspartamiT Secvlas); 3´ UTR (a
TGTG delecia, romelic xdeba me-15 egzonis ukanasknel 55-e nukleotidur
wyvilSi, 15:1729+55del4) - polimorfizmi msoflios sxvadasxva populaciaSi
araTanabrad aris gavrcelebuli da araTanabrad asocirdeba tuberkulozTan.
5´8----- -----//------- ----------- ------//------ -------- 3´
5´(GT)n INT4 D543N 3´UTR
sqema 1. SLC11A1polimorfuli lokusebi
magaliTad, aziuri qveynebis populaciebSi gamovlinda 5’(GT)n, 3′UTR,
D543N lokusebis polimorfizmis asociaciuri kavSiri tuberkulozTan, maSin,
roca evropul populaciaSi mocemuli oTxi lokusidan arc erTi maTganis
polimorfizmTan ar dafiqsirda tuberkulozis asociaciuri kavSiri.
ეგზ.15 ეგზ.5 ეგზ.2 ეგზ. 1
124
yvelaze dabali sixSiriT tuberkulozis dros meoTxe intronSi (INT4)
momxdari mutaciebi fiqsirdeba (Takahashi, 2008; Li 2006). zangisa da misi
TanamSromlebis (Zhang et al., 2005) mixedviT, INT4 da D543N-is polimorfizmi
asociaciur kavSirSia inficirebis Semdeg tuberkulozis mZime formis
progresirebasTan. SLC11A1-s zemoT aRniSnul alelTa polimorfizmis
asociaciuri kavSiri tuberkulozis mZime formasTan dadasturebuli iqna
tarakaSis da misi TanamSromlebis mier iaponur populaciaSi. amave avtorebis
mier Catarebuli kvlevis safuZvelze gamoiTqva varaudi, rom SLC11A1–s
polimorfizmi asociaciur kavSirSia tuberkulozis wamalrezistentul
formasTan (White et al., 1994; Liu et al., 1995; Takahashi et al., 2007).
Cvens mier kvleva Catarebuli iqna filtvis tuberkulozis
wamalrezistentuli formiT daavadebul pacientebSi. sakvlev jgufs
warmoadgenda 18-dan 67 wlamde asakis 80 pacienti - 21 qali da 59 mamakaci,
romlebic rezistentulni iyvnen, sul mcire, izoniazidisa da rifampicinis
mimarT, maTi 37.5% rezistentuli iyo eTanbutolis, izoniazidis,
pirazinamidis da rifampicinis mimarT, 15% - eTanbutolis, izoniazidisa da
rifampicinis mimarT, 38% - izoniazidis da rifampicinis mimarT, xolo 5%-
eTanbutolis mimarT. pacientTa 50%-ze mets mkurnalobdnen meore rigis
preparatebiT: fluoroqinolebiT (levofloqsacini, ciprofloqsacini da a. S.)
da TioamidebiT (ZiriTadad eTionamidi), aseve damatebiT – aminoglikozidebiT
(amikacini, kanamicini) da polipeptidebiT (ZiriTadad kapreomicini).
daavadebulTa 49% pirveladi wamalrezistentobiT, xolo 51% meoradi
rezistentobiT iyo avad. rezistentuli tuberkulozis mqone pacientTa
82.5%-s daudginda daavadebis Ria forma. pacientTa 50%-s - infiltraciuli,
23% - diseminirebuli, 18,75% - fibro-kavernozuli, 6.25% - kavernozuli da
5% - infiltraciul-diseminirebuli formiT iyo daavadebuli.
sakontrolo variantad aRebuli iqna wamlis mimarT sensitiuri
tuberkuloziT daavadebuli 18-dan 64 wlamde asakis 40 pacienti - 12 qali
da 28 mamakaci. sensitiuri tuberkulozis mqone 77.5% - baqteriagamoomyofi
125
iyo (mgb+). pacientTa 45-45% daavadebis diseminirebul da infiltraciul, xolo
danarCeni 10% kavernozul da fibrokavernozul formaze modioda.
SLC11A1-is polimorfuli variaciebis gamosavlenad eleqtronuli
bazidan aRebuli iqna genis saanalizo monakveTi (sqema. 2).
SLC11A1 genis D543N lokusi, sadac mutaciiT gamowveuli
erTnukleotidiani cvlileba iwvevs genis mier kodirebuli cilis
(moTavsebulia endosomebSi/ lizosomebSi) molekulaSi aspartamis mJavis
asparaginiT Canacvlebas. amis gamo irRveva rkinis ionebis cvla da aRniSnuli
cvlileba gavlenas axdens makrofagebis funqciur aqtivobaze.
saZiebeli ubnis amplifikaciisTvis SerCeuli iqna praimerebi da
gansazRvrul iqna restriqciuli fermentis (Hpy188I) samizne saitebi (sqema. 2):
SLC11A1-s sakvlevi regioni (PCR produqti)
praimeri 1 (Frw)
restriqciuli saiti
GAGCAAAACTCTATTTCGAAAAAAAAAAAAAAAGTTTATCTCTGCCTTTCCATCTC
CTGTATGCTCTTCCTACATAAGGTAGGAAGCCCATTGGCCAGACTGTCTAGTAAATGTA
GTCTGAGACGACAGACAAATGTAGTCTGAGACGACAGGCAAATAACCG
GCCCACCCTTAATGAAGGATCATCTCCTCCCCATAGGTGCCCCGCAC
CGTCCTCTGGCTGACCATCGAGCTAGCCATTGTGGGCTCCRACATGC
AGGAAGTCATCGGCACGGCCATTGCATTCAATCTGCTCTCAGCTGGAC
GGTACCACCCCAGTGTACCCCAACTCTTCAGGCCAGGCAGAGAACAGCTGCTGCTACT
TCCCCCCCTAACCAGTCCCTCCCAGAGTCTATTTTATCCTGCTGTCCCCTCTGAAGCAGG
GCTGCTGCCCTGTTTTCCAGAAATGTAAAGTGACTTGTCTAAAGTCACACAGATGTGAG
TCATGCAGGACTTTGGGAC
restriqciuli saiti praimeri 2 (Rev)
sqema. 2. SLC11A1 genis monakveTi, romelic moicavs saanalizo 543 kodons. PCR -produqti
moicavs 194 nukleotidur wyvils
126
SLC11A1 genis 543-e kodonSi polimorfizmi vlindeba azotovani fuZeebis
CanacvlebiT, romlebic SLC11A1-s D543N alelSi qmnian GG, AA, AG variaciebs.
sakvlevi dnm damuSavebuli iqna Hpy188I restriqtaziT.
Hpy188I- restriqtaziT damuSavebis Semdeg:
GG: 23 (kontroli) + 108 + 61
AA: 23 (kontroli) + 169
AG: 23 (kontroli) + 169 + 108 + 61
cxr.5. RFLP-is mosalodneli Sedegebi
restriqciuli endonukleazas moqmedebis sakontrolod SerCeul iqna
erTi restriqciuli saiti, romlis produqtic gelze dnm-is 23
nukleotiduri fuZis mqone fragmenti unda yofiliyo. SLC11A1 genis D543
lokusSi GG alelis arsebobis SemTxvevaSi gelze unda gamovleniliyo
sakontrolo variantis-23 + 108 da 61 nukleotiduri fuZis Semcveli
fragmentebi, GA alelis SemTxvevaSi - sakontrolo variantis-23 + 169, 108 da 61
nukleotiduri fuZis mqone frgmentebi, xolo AA alelis SemTxvevaSi - mxolod
sakontrolo variantis-23 + 169 n.f.-is mqone fragmentebi (cxr. 5).
rogorc SLC11A1 genis eleqtroforegramidan Cans (sur.14), rom
aRniSnuli geni 543 kodonSi iZleva 23, 61 da 108 nukleotiduri fuZis mqone dnm-
is fragmentebs, sadac pirveli sakontrolo variantia, xolo 61 da 108 nf-is
mqone fragmentebi - GG alelis damadasturebeli fragmentebi.
127
sur.14. D543N lokusi restriqciuli endonukleaziT damuSavebis Semdeg (isrebiT naCvenebia RFLP-
-is Sedegebi agarozas gelze. isris gaswvriv cifrebiT naCvenebia dnm fragmentis nukleotiduri fuZis raodenoba)
SLC11A1 genSi momxdari mutaciebi, romlebic genis polimorfizms
ganapirobeben, xels uSlian fagosomebis momwifebas da asociaciuri kavSiri
gaaCniaT tuberkulozis mimarT organizmis mgrZnobelobasTan (Greenwood 2000;
Bellamy et al., 1998; Cevino et al., 2000; Ryu et al., 2000; Gao et al.,2000), maSin, roca sxva
mkvlevarebi aseTi tipis kavSiris arsebobas ar adastureben (liaw et al., 2002;
Delgado et al., 2002; El Baghdadi et al., 2003; Soborg et al.,2002; Puzyrev et al., 2003).
kvlevis Sedegad miRebuli erTgvarovani eleqtroforezuli speqtri
miuTiTebs, rom SLC11A1 geni D543N lokusSi genetikuri polimorfizmiT ar
xasiaTdeba tuberkuloziT daavadebuli qarTuli populaciaSi. rogorc
multirezistentul, ise sensitiur pacientTa absoluturi ricxvi atarebs
mxolod D543 GG alels (sur.14).
literaturul monacemebze dayrdnobiT myarad SeiZleba iTqvas, rom
SLC11A1 genis sxvadasxva polimorfuli variaciis korelacia tuberkulozis
winaswarganpirobebulobasTan eTnikuri specifikurobiT xasiaTdeba.
daavadebis klinikur formebTan mimarTebaSi Catarebuli kvlevis Sedegad
gamovlinda, rom D543N A aleli da 3’UTR lokusis polimorfizmi kavSirSia
filtvSi Rru dazianebebis ganviTarebasTan da Sesabamisad, kavernozul
formasTan iaponur populaciaSi (Abe et al., 2003), xolo afrikul populaciaSi
23ნფ
108ნფ
61ნფ
128
gamovlinda 5’(GT)n, INT4 da D543N lokusebis polimorfizmis asociaciuri
kavSiri tuberkulozTan. veranairi asociaciuri kavSiri ver iqna napovni
SLC11A1 alelebis polimorfizmTan, rogorc filtvis, ise filtvgare
tuberkulozTan daniur populaciaSi (Soborg et al.,2002).
Cvens mier Catarebuli kvlevebidan gamomdinare, SeiZleba davaskvnaT,
rom SLC11A1 genis D543N lokusis polimorfizmi qarTul populaciaSi ar
asocirdeba filtvis tuberkulozis multirezistentul formasTan da ar
monawileobs daavadebisadmi organizmis winaswarganpirobebulobaSi. kvlevis
Sedegad miRebuli monacemebi emTxveva soborgis, delganos da sxvaTa (Soborg et
al.,2002; liaw et al., 2002; Delgado et al., 2002; El Baghdadi et al.,2003; Puzyrev 2003) mier
miRebul Sedegebs.
vfiqrobT, SLC11A1-s polimorfizmis sruli analizisTvis qarTul
populaciaSi aucilebelia aRniSnuli genis sxva lokusebis polimorfuli
variaciebis Ziebac, aseve, sxva kandidati genebis Zieba da analizi, vinaidan
cnobilia, rom arsebobs tuberkulozis winaswarganpirobebulobaze moqmedi
sxva genetikuri faqtorebi (Medzhitov, 2001; Krutzik et al, 2001; Moore et al., 2001; Hill
2006; Taype et al., 2006; Niimi et al., 2002; Henao et al., 2006; Oral et al., 2006; Mak et al., 2007;
Taype et.al., 2010; Prithvi et.al., 2011), romlebic, aseve, maRali eTnospecifikurobiT
xasiaTdebა.
129
daskvnebi
1. filtvis tuberkuloziT daavadebul sakvlev qarTul populaciaSi
dadgenil iqna daavadebis asociacia O(I) da B(III) fenotipur jgufebTan.
aRniSnuli jgufebis matarebeli individebi tuberkulozis mimarT
mgrZnobelobiT gamoirCevian da miekuTvnebian daavadebis ganviTarebis risk-
jgufebs. A(II) fenotipuri jgufis matarebeli individebi SedarebiT maRali
imunuri mdgradobiT xasiaTdebian filtvis tuberkulozis mimarT.
2. sensitiuri tuberkuloziT daavadebis maRali riskis jgufebs
warmoadgens O(I) da B(III) jgufis fenotipis matarebeli individebi, xolo
wamalrezistentuli formis SemTxvevaSi - mxolod O(I).
3. ABO sistemis q alelis matarebloba qarTul populaciaSi
korelaciaSia daavadebis mimarT organizmis mdgradobasTan. janmrTel
populaciaSi igi 1.27-jer maRali sixSiriTaa warmodgenili daavadebulTan
SedarebiT, xolo r alelis matarebloba SeiZleba CaiTvalos, rogorc
sensitiuri, ise wamalrezistentuli tuberkulozis mimarT mgrZnobelobis
indikatorad. azerbaijanel pacientebSi, piriqiT, q(B) aleli asocirdeba
daavadebis mgrZnobelobasTan, radgan igi donorulTan SedarebiT 2.3-jer
maRali sixSiriT tuberkulozur pacientebSi fiqsirdeba. p alelis 2,51-jer
maRali sixsSire donorebSi asocirdeba aRniSnuli alelis mdgradobasTan
filtvis tuberkulozis mimarT. ABO sistemis alelebis gansxvavebuli
asociacia daavadebasTan, SesaZloa, qarTuli da azerbaijanuli populaciebis
eTnospecifikurobiT iyos ganpirobebuli.
4. filtvis tuberkuloziT daavadebul qarTul populaciaSi Rh+
faqtori, azerbaijanul populaciaSi ki - Rh- faqtori dominirebs. rezus
sistemis madeterminirebeli RhD, RhC da RhE alelebi gansxvavebul
korelacias avlenen filtvis tuberkulozis sxvadasxva formasTan. RhC
130
aleli mgrZnobiarea sensitiuri, xolo RhE aleli - daavadebis
wamalrezistentuli formis mimarT. tuberkulozisadmi sensibilobiT
gamoirCeva individebi rezus sistemis Cde, cdE da CDe haplotipebiT, xolo
daavadebisadmi mdgrad haplotipebs warmoadgens cde, cDe da cDE haplotipebi.
5. kvlevis Sedegad dadgenil iqna, rom rezus sistemis CcDEe (19,7±2,7)
fenotipi, romelic daavadebul populaciaSi 2,46-jer maRali sixSiriT
fiqsirdeba donorulTan (8±2,7) SedarebiT, mniSvnelovan asociaciur kavSirs
avlens filtvis tuberkulozis orive formasTan.
6. tuberkulozTan myarad korelirebs MN sistemis q aleli da,
Sesabamisad, M antigeni. aqedan gamomdinare, maTi matarebeli individebi
miekuTvnebian tuberkulozis maRali sensibilobis jgufs, xolo p alelis da,
Sesabamisad, N antigenis matarebloba daavadebis mimarT erTgvar
„damcvelobiT“ niSans warmoadgens saqarTveloSi mcxovreb filtvis
tuberkuloziT daavadebul, rogorc qarTul, ise azerbaijanul populaciaSi.
7. Seswavlil pacientebSi daavadebis formis (kerovani, infiltraciuli
rRvevis fazaSi, fibro/kavernozuli) simZimesTan erTad specifikuri jamuri
antisxeulebis done matulobs. savaraudod, daavadebis fazis sirTulesTan
erTad adgili aqvs imunostimulacias, rac antisxeulebis sinTezis matebaSi
gamoixateba. es SeiZleba, gamoyenebul iqnes daavadebis fazebis
diferencirebul diagnostikaSi, rogorc damatebiTi informacia.
8. specifikur antisxeulTa titri xangrZlivad namkurnalev pacientebSi
(metwilad, wamalrezistentuli pacientebi, romlebSic baqteriis koncentacia,
savaraudod, maRalia) pirvelad pacientebTan (axal dawyebuli mkurnalobis an
aranamkurnalevi) SedarebiT maRalia, radgan imunuri sistema daavadebis
simZimes antisxeulebis matebiT pasuxobs. savaraudod, antituberkulinuri
jamuri antisxeulebis koncentraciis Seswavla efeqturi iqneba mkurnalobis
monitoringis TvalsazrisiTac.
131
9. antisxeulebis maRali titri gansakuTrebiT vlindeba IgG-s
koncentraciis matebaSi. aRniSnuli imunoglobulinis done daavadebis,
rogorc sensitiuri, ise rezistentuli formisas sagrZnoblad maRalia
sakontrolo jgufTan SedarebiT (P<0.001). es exeba, rogorc mdedrobiTi, ise
mamrobiTi sqesis pacientebs. aRniSnuli monacemi SesaZlebelia, gamoyenebul
iqnes, rogorc damatebiTi sadiagnostiko saSualeba.
10. filtvis tuberkuloziT daavadebul pacientebSi specifikuri
antituberkulinuri antisxeulebis gamovlena gansakuTrebiT mniSvnelovania
rRvevis stadiaSi myofi infiltraciuli tuberkulozisas da daavadebis
fibrozul-kavernozuli formis dros. pacientis SratSi arsebuli
specifikuri antisxeulebis titris gansazRvra daavadebis adreul stadiaze
diagnostirebis saSualebas iZleva da SeiZleba, gamoyenebuli iqnes, rogorc
damatebiTi diagnostikuri meTodi.
11. humoruli imunuri pasuxi (imunoglobulinebis saerTo done)
filtvis tuberkulozis sensitiur da wamalrezistentul formebs Soris
mniSvnelovan sxvaobas ar iZleva da organizmi daavadebis orive formis dros
aviTarebs msgavs imunur pasuxs, rac gamoixateba IgG-is donis mniSvnelovan
matebaSi.
12. SLC11A1 geni, romlis polimorfuli variaciebi zogierT eTnikur
populaciaSi asocirdeba filtvis tuberkulozTan da gansazRvravs
daavadebisadmi midrekilebas, filtvis tuberkuloziT daavadebul qarTul
populaciaSi polimorfulobas ar avlens. am mimarTebiT gamokvleuli
evropuli populaciebis msgavsad, SLC11A1 genis D543N-is lokusis
polimorfuloba ar asocirdeba rezistentul tuberkulozTan qarTul
populaciaSi da aziuri populaciebisgan gansxvavebiT, ar gansazRvravs
daavadebisadmi winaswarganpirobebulobas.
132
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