Moleculebiological analysis of HLA class II in autoimmune hepatitis.

1. 为了研究日本患者自身免疫性肝炎与HLA等位基因之间的关系，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法进行血清学分型和II类基因分型。血清学分型显示HLA-B54、-Dr53和-DQ4与自身免疫性肝炎显著相关（88.7%）。在PCR-RFLP分型中，患者与dr4阳性对照之间的Dw频率。DQA1**0301和DQB1**0401的显著增加与DR4的连锁不平衡有关。6例dr4阴性患者有DR2，但DR2阳性对照的频率无显著差异。没有DQB1等位基因与自身免疫性肝炎显著相关。这些发现表明，仅存在于DR4 B1分子（DR2上的Arg和DR4上的His）的第13位的碱性氨基酸有助于日本人对自身免疫性肝炎的易感性。我们明确了自身免疫性肝炎（AI-CAH）患者与自身抗体和高球蛋白血症阳性的C型慢性活动性肝炎（C- cah）和B型慢性活动性肝炎（B- cah）患者的临床和免疫遗传学差异。输血、静脉药物滥用和纹身史在C-CAH患者中很常见，而在AI-CAH患者中却很少见。AI-CAH表现为厌食、嗜睡、黄疸、高热及肝外表现等严重的主观症状，生化指标出现严重异常。HLA-DR4最常与AI-CAH相关（89%），6例dr4阴性患者DR2阳性。HLA-DNA分型显示，患者与DR4阳性对照之间DR4相关dw等位基因的频率无显著差异。这些发现提示，仅存在于DR2和DR4-B1分子的13位碱性氨基酸可能与日本人对自身免疫性肝炎的易感性有关。因此，我们认为AI-CAH是一种遗传限制性疾病，不同于C-CAH是一种病毒感染性疾病。少

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