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Immunogenetic analyses of autoimmune chronic active hepatitis in Japanese

Research Project

Project/Area Number 02807076
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionThe Jikei university school of medicine

Principal Investigator

AIZAWA Yoshio  The jikei university school of medicine, Internal medicine (1) Assistant, 医学部・第1内科, 助手 (90147273)

Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
Keywordsimmunogenetics / autoimmune / HLA-DR4 / HLA-B35 / hepatitis / 自己免疫性肝炎 / HLA / DR4サブタイプ / DRB鎖 / SSO法 / PCR / オリゴヌクレオタイド
Research Abstract

The immunogenetic background of Japanese autoimmune type of chronic active hepatitis was studied. The HLA antigens of 29 chronic active hepatitis whose gamma-globlin level was over 2.5g/dl and serum autoantibody was positive were examined. In 29 patients, 14 were HCV-RNA negative (pure AIH) and 15 were HCV-RNA positive (type C AIH).
In 14 pure AIH group, all patients have HLA-DR4 and 9 patients have HLA-Dw4 which was closely associated to HLA-DR4. The frequency of HLA-DR4 and HLA-DQw4 in pure AIH was significantly higher than healthy Japanese controls (p<0.01). The frequency of other HLA antigens was not statistically increased in pure AIH. In 15 type C AIH, not HLA-DR4 (frequency, 60%) but HLA-B35 was significantly increased in frequency compared with normal Japanese controls. These data suggested that in view of immunogenetics, the pathogenesis of pure AIH differed from type C AIH.
Further molecular analyses were performed on HLA-DR4 gene obtained from pure AIH patients. The exon 2 of DR beta gene in HLA-DR4 was amplified by PCR and then, subtype specific restriction fragment polymorphysms were analyzed using restriction enzyme. HLA-DR4 was classified into several subtypes according to the differences of DNA and deduced amino acid sequences. 1 In our study, specific HLA-DR4 subtypes were found in pure AIH. The common sequences in these subtypes ware found in the third hypervariable region in the exon 2 of DR beta gene. Because the nature of amino acid in this hypervariable region was thought to be important for the recognition of T lymphocyte, we concluded that the sequences of this region may critical for disease susceptibility in pure AIH.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 相沢 良夫: "自己免疫性肝炎の免疫遺伝学的背景" MINOPHAGEN MEDICAL REVIEW. 37. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 銭谷 幹男: "慢性肝炎の免疫学的背景" 肝細胞障害と肝細胞増殖. 55-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yoshio Aizawa: "Immunogenetic background of autoimmune hepatitis" Minophagen Medical Review. 37. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Mikio Zeniya: "Immunological background of chronic hepatitis" Hepatocyte Damage & Hepatocyte Proliferation. (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 相沢 良夫: "自己免疫性肝炎の免疫遺伝学的背景" MINOPHAGEN MEDICAL REVIEW. 37. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 銭谷 幹男: "慢性肝炎の免疫学的背景" 肝細胞障害と肝細胞増殖. 55-61 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 渡辺 文時: "自己免疫性肝炎発症に関するHLA抗原の解析 ー特に疾患感受性に関与するDR4サブタイプの分子生物学的検討ー" 肝臓. 31. 270 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 銭谷 幹男: "自己免疫性肝炎における免疫遺伝学的背景" 厚生省難治性の肝炎調査研究班平成2年度報告. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 銭谷 幹男: "慢性肝炎の免疫学的背景" 肝と免疫. (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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