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Helicobacter pylori 感染と自己免疫疾患, 特に免疫 . pylori 感染と自己免疫疾患,特に免疫血小板減少性紫斑病 3 平成22年1月20日 なかで696名の患者の治療成績を評価し,完全緩解は

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Helicobacter pylori

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Key words : Helicobacter pylori, autoantibody, autoimmune disease, thrombocytopenic purpura,Lewis antigen

Campylobacter jejuniacute inflammatory demyelinat-ing polyneuropathy IgA Haemophilus parainfluenzaeMycobac-terium paratuberculosisM. paratuberculosis20 Helicobacter pyloriH. pyloriO Lewis Lewis H. pylori H. pylori

1 H. pylori1989 Negrini H. pylori

H. pylori H. pylori H. pyloriH. pylori 65.5 IgG H. pyloriH. pylori

aGasbarrini

Idiopathic thrombo-cytopenic purpuraITPImmune thrombocytopenic purpura H. pylorib 55 H. pylori

H. pylori 88c 40 H. pylori 83

d H. pylori 89

4668550 65

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Fig. 1 Effectiveness of H. pylori eradication therapy for ITP patients(Modified from reference 15)

eH. pylori

2 H. pylori H. pyloriCRPf 55 H. pylori

gWegener

36 25 H. pylorih1B

H. pyloriHbA1c B IgG Sjogren Schonlein-Henoch

H. pylori ITP

H. pylori H. pylori

2ITP H. pylori1998 Gasbarrini H. pylori

ITPH. pylori ITP78 ITP H. pyloriH. pylori ITP2007 H. pylori the Maastricht IIIConsensus Report ITP H. py-lori2009 Stasi ITP H. pylori 25 1,555 ITP

H. pylori 3

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696 42.7 50.3 ITP H. pylori H. pyloriITPFig. 1 ITP ITP H. pyloriITP ITP H. pylori ITPH. pyloriITPYamamoto ITP

3ITP aCD40bCD40c cba H.pylori ITPITP

ITP H. pyloriH. pylori H.pylori

KOLPSHKOELISA

3H. pyloriO Lewis Lewis 1996 Aspinall H. pylori NCTC 11637 O

N-acetyllactosamineLacNAc Lewis Lex 2P466 MO19 OP466 O Lex LeyMO19 Ley H. pylori Lewis H. pyloriFig. 2

H. pylori Lex Ley H. pylori Lewis Lewis H. pylori IgG Lex LeyELISA Lewis ELISA Le H1K1-ATPase Ley

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Fig. 2 Lewis blood type structure (Lea, Leb, Lex, Ley) and their biosynthetic pathway in H. pylori

Lex Ley LeyAppelmelk Lewis 152 80.9 Lex LeyH1Lewis H. pyloriCagA VacA

ABO C. jejuniO

H. pylori Lewis

H. pylori 5

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Fig. 3 Domain structure of fucT2 ( 1, 2 fucosyltransferase) geneLength of poly C and poly A regions are variable even among colonies (subclones) originated from the same strain.

(Our unpublished results)

Le-wis 22 Lewis Gal1,4GlcNAc 1,3 1,4FucT1 1,2FucT2Wang fucT2Cpoly CDNAframe shiftFrame shift poly C FucT2 LeyFig. 3phase variationfucT1 H. pylori Lex Ley

Fig. 4 Lewis

Lewis IgG Lewis H. pyloriITPLewis HK-ATPase ITP

H. pylori

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Fig. 4 Expression of Lex and Ley in clinically isolated H. pylori strains 1 - 33 (Our unpublished results)

H. pyloriH. pylori Lewis Lewis H. pylori1ITP

H. pylori2 Lewis Lewis

3 H. pyloriO

O4

H. pylori

H. pyloriO

1Yuki N, Yoshino H, Sato S, Miyatake TAcuteaxonal polyneuropathy associated with anti-GM1 antibodies following Campylobacter enteri-tis. Neurology 19904019002.

2Suzuki S, Nakatomi Y, Sato H, Tsukada H,Arakawa MHaemophilus parainfluenzae antigenand antibody in renal biopsy samples and se-rum of patients with IgA nephropathy. Lancet1994343126.

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4Negrini R, Lisato L, Zanella I, Cavazzini S,Gullini S, Villanacci V, et al.Helicobacter pyloriinfection induces antibodies cross-reacting withhuman gastric mucosa. Gastroenterology 199110143744.

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6Gasbarrini A, Franceschi F, Tartaglione R, Lan-dolfi R, Pola P, Gasbarrini GRegression of

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autoimmune thrombocytopenia after eradicationof Helicobacter pylori. Lancet 199835278.

7Di Campli C, Gasbarrini A, Nucera E, Fran-ceschi F, Ojetti V, Sanz Torre E, et al.Benefi-cial effects of Helicobacter pylori eradication onidiopathic chronic urticaria. Dig Dis Sci 199843612269.

8Gasbarrini A, De Luca A, Fiore G, Gambrielli M,Franceschi F, Ojetti V, et al.Beneficial effectsof Helicobacter pylori eradication on migraine. He-patogastroenterology 19984576570.

9Gasbarrini A, Massari I, Serricchio M, Tondi P,De Luca A, Franceschi F, et al.Helicobacter py-lori eradication ameliorates primary Raynaudsphenomenon. Dig Dis Sci 19984316415.

10Zentilin P, Seriolo B, Dulbecco P, Caratto E, Iiri-tano E, Fasciolo D, et al.Eradication of Helico-bacter pylori may reduce disease severity inrheumatoid arthritis. Aliment Pharmacol Ther200216712919.

11Migneco A, Ojetti V, Specchia L, Franceschi F,Candelli M, Mettimano M, et al.Eradication ofHelicobacter pylori infection improves blood pres-sure values in patients affected by hyperten-sion. Helicobacter 200385859.

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13Imai J, Yamada T, Saito T, Ishigaki Y, HinokioY, Kotake H, et al.Eradication of insulin resis-tance. Lancet 2009374264.

14Malfertheiner P, Megraud F, OMorain C, Baz-zoli F, El-Omar E, Graham D, et al.Currentconcepts in the management of Helicobacter py-lori infection : the Maastricht III Consensus Re-port. Gut 20075677281.

15Stasi R, Sarpatwari A, Segal JB, Osborn J, Evan-gelista ML, Cooper N, et al.Effects of eradica-tion of Helicobacter pylori infection in patientswith immune thrombocytopenic purpura : a sys-tematic review. Blood 2009113123140.

16Yamamoto F, Narimatsu H, Ito M, Yamashita S,Kurahashi S, Sugimoto T, et al.Prediction ofclinical outcome in patients with idiopathicthrombocytopenic purpura by evaluating bonemarrow clot CD20+ B lymphocytes and mor-phological changes of megakaryocytes. J ClinExp Hematop 2008481115.

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Helicobacter pylori Infection and Autoimmune Disease Such as Immune Thrombocytopenic Purpura

Michio OHTADepartment of Bacteriology, Nagoya University Graduate School of Medicine

Helicobacter pylori infection is implicated in the pathogenesis of extradigestive diseases such as acne ro-sacea and idiopathic chronic urticaria and autoimmune diseases such as autoimmune gastric atrophy, rheu-matoid arthritis, anti phospholipid antibody syndrome, autoimmune thyroiditis, Sjoegren syndrome, Henoch-Schoenlein purpura, and Type B insulin resistance syndrome. H. pylori eradication ameliorated the conditionin some, but not all, of those with these autoimmune diseases. Recent studies primarily in Italy and Japanfound that H. pylori eradication in those infected with chronic immune thrombocytopenic purpura (ITP) re-sults in a persistent platelet count increase in over half of those treated, suggesting that although pathoge-netic mechanisms underlying the relationship between H. pylori infection and autoimmune disease remainunclear, yet-unknown immunological events induced by H. pylori infection almost certainly occur in the de-velopment of autoimmune response.

A majority of isolated H. pylori strains express human Lewis (Lex andor Ley determinants and in somestrains, Lea, Leb, sialyl-Lex), and H determinants in the O-chain of the surface lipopolysaccharide. Previousstudies showed that this molecular mimicry helps the bacterium evade host responses while evokingautoantibody responses to Le antigens. The anti-Ley autoantibody is also reported to promote H. pylori adhe-sion to gastric epithelial cells, leading to development of gastric atrophy. Moreover, one can hypothesize thatanti-Le autoreactive antibodies induced by H. pylori infection are involved in the development of autoim-mune diseases, although no clinical studies showing that anti-Le immune responses are involved in the etiol-ogy of these autoimmune diseases have been conducted. Proving this hypothesis would require quantitativeand qualitative analysis of autoantibodies and T cell functions to Le antigens. High frequent phase variationof Le structures in the O-polysaccharide of H. py