| 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)
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| 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.
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