1993 Fiscal Year Final Research Report Summary
Moleculebiological analysis of HLA class II in autoimmune hepatitis.
| Project/Area Number |
03454227
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Shinshu University |
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Principal Investigator |
KIYOSAWA Kendo The Second Department of Internal Medicine, Shinshu University School of Medicine, Associate Professor, 医学部・第2内科学講座, 助教授 (30020829)
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| Co-Investigator(Kenkyū-buntansha) |
INOKO Hidetoshi Department of Molecular Life Science, Tokai University School of Medicine Profes, 医学部・分子生命科学講座, 教授
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| Project Period (FY) |
1991 – 1993
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| Keywords | autoimmune hepatitis / HLA class-II / disease susceptibility / DRB1-chain / hepatitis C virus |
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| Research Abstract |
1. To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP)method. Serologicaltyping showed that HLA-B54, -Dr53, and -DQ4 were significantly associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of Dw between the patients and thecontrols who were DR4-positive. The significant increase observed in DQA1**0301 and DQB1**0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-positive controls. No DQB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.
2
… More
. We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis(C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH.The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH.HLA-DR4 was the most frequently associated with AI-CAH(89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only DR2 and DR4-B1 molecules, may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted disease and different from C-CAH which is a viral infectious disease. Less
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