Click here to load reader

免疫缺陷病 ( immunodeficiency disease )

  • View
    103

  • Download
    4

Embed Size (px)

DESCRIPTION

免疫缺陷病 ( immunodeficiency disease ). 上海交通大学医学院附属新华医院 儿内科 陈嫕. 小儿免疫系统发育. 单核/巨噬细胞 中性粒细胞 T 淋巴细胞及细胞因子 B 淋巴细胞及 Ig 补体和其他免疫分子. 新生儿出生时 T 淋巴细胞. T 细胞总数少 CD4+T 细胞相对较多, CD4/CD8 比例高达 3~4 Th2 细胞功能相对亢进,易患过敏性疾病 CD45RA+T 细胞比例较大, CD45RO+T 细胞比例较少 细胞因子产生不足: IFN- γ 和 IL-4 等. 新生儿出生后 IgG 的变化. 可达正常成人水平 - PowerPoint PPT Presentation

Text of 免疫缺陷病 ( immunodeficiency disease )

  • (immunodeficiency disease)

  • /TBIg

  • TTCD4+TCD4/CD83~4Th2CD45RA+TCD45RO+TIFN-IL-4

  • IgG6IgG3~6IgG1IgG60%6100% IgG

  • IgGIgG1IgG2IgG3IgG4 IgGIgG15IgG310IgG2IgG414

  • IgMIgM200-300mg/L4-7IgMIgM IgM

  • IgA120%12IgA50mg/L2-3IgAIgA

  • g/L1995:413

    IgGIgAIgM5.190-10.790(8.490)0.001-0.018(0.0009)0.018-0.120(0.069)4m-3.050-6.870(4.970)0.110-0.450(0.280)0.310-0.850(0.580)7m-4.090-7.030(5.560)0.210-0.470(0.340)0.330-0.730(0.530)1y-5.090-10.090(7.590)0.310-0.670(0.490)0.980-1.780(1.380)3y-6.600-10.39(8.240)0.580-1.000(0.790)1.100-1.800(1.450)7y-7.910-13.070(10.720)0.850-1.710(1.280)1.200-2.260(1.730)12y-8.270-14.170(11.220)0.860-1.920(1.390)1.220-2.560(1.890)

  • =

  • immunodeficiencyID

  • 50%20%18%T10%2%

  • 1/10000 198119831/80001/10000250025003~8301980150

  • =

  • XIgAIgM-

    SLEITPSLE0.01%~14%

  • 100-300

  • 8 2 2 2 PID

  • 1 (A-T)

  • IgGIgMIgA BX NBT

  • CD3CD4CD8 TCD19 BCD56/16 NK IgG1~4

  • /

    IL-2IL2RIFNIFNR BTK CD40LWASP

  • XIgA

  • X-linked agammaglobulinaemiaXLA Bruton19521993Bpre B-cell cytoplasmic tyrosine kinasebtk BBB180

  • 4 ~ 6

  • IgG < 2g/L (
  • T

  • BNK

  • 62145-6215562155-62145Exon10RExon10FBtkcDNA mutation:989_999delTGACTCGGAGTinsGGTGGTATTCCAAA

    Codon change:MTRS286_289RWYSK

    Mother status:carrier

  • IgMIgGIgABIgG?XLA

    6mo//B/

    1~2

  • PIDCVID Common Variable ImmunodeficiencyCVID IgG
  • CVID

    IgMIgGIgATXLA

    6mo//BCVID

  • XIgA

  • 1/500~15001/185001/5000~10000Th2BIgA

  • IgA0.05g/LIgMIgGIgAIgAIVIGIgA

  • XIgASCID

  • DiGeorge 196480%~90%Digeorge22q1122q11CATCH22

  • CATCH 22Cardiac defectsAbnormal faciesThymus hypoplasiaCleft palateHypocalcemia

  • --T

  • 14DiGeorge

  • 610g

    4g

  • DiGeorge

  • XIgA

  • SCIDXSCIDSCIDGVHR1 Severe combined immunodeficiencySCID

  • T- B+NK-Ig-XSCID50%~60%IL-2IL-4IL-7IL-9IL-15cSCIDJAK3JAK3c

  • RAG-1RAG-2TB50%ADAT-B-NK+Ig-

  • Figure: a photo of a patient with SCID candida albicans in the mouth86moT-B+NK-Ig

  • Figure: a photo of a patient with SCID GVHD and BCG accination43

  • T

  • BNK

  • Molecular Diagnosis of X-SCID in Patient 1 IL2RG gene PCR direct sequencing IVS6-17Deletion in patientNormal control: Intron 6 IVS7-11 Deletion in patientNormal control: Intron 7 487bp deletionPatient 1: deletion between Intron 6 and intron 7Deletion mutation from intron 6 to 7 including exon 7 and 2 primer site (IVS6-71 to IVS7-11del487) Predicted frameshift start at arginine 285 with stop codon (TAA)created at position 342, predicted premature termination (R285fsX342)

  • Carrier diagnosis in IL2RG deletion (XSCID) Patient 1 PCR-agarose gel electrophoresis Causative gene: IL2RG in X-chromosome

    PCR amplified for each exon for sequencingNo PCR product for amplification of exon 6, 7 and 8Suspected large deletion, try other primer pairs combinationDeletion mutation including exon 7 and 2 primer site found (IVS6-71 to IVS7-11del487) Mother diagnosed as heterozygous carrier by PCR directly

  • IgMHyper IgM syndromeHIGMT+CD40L-B+IgMIgGX70%TCD40LTCD40L

  • CD40CD40LTCRMHC-AgIgMIgGIgAIgEIL-2IFN-T-B

  • patientcontrolCD40LFig. CD40 ligand expression induced by PMA+IM in paitent with HIGM

  • CD40 ligand gene mutations identified in this studyExon5 cDNA mutation: 672-675delCTCACodon change: L205fsX240Mother status: not carrier11319495-1131949411319492-11319495

  • Wiskott Aldrich Syndrome Patient Photothrombocytopenic purpura eczema

  • WASVit DTTGVHR2000~3000radCMVCMV

  • B IVIGT ADASCID 11

  • IVIG80%IgG400mg/kg/mIgG5g/L

  • ADA-PEG15~30u/ug 1~2 PNPADA IL-2SCID

  • HLAHLA

  • ADA XL-SCID 11 ZAP70JAK3 LAD WASPNPMHC IICGDXLA

  • **TT80%CD45RA+TCD45RO+T*IGG4 IGG1IGG3 IGG2IGG4*IGG1IGG3NKFcADCC Arginine Prime pair

    CD40LBCD40BIgMIgGIgAIgETCD40LCD40IL-12 CD40LCD40LCD40CD40T