Immunogenetic studies of autoimmune chronic active hepatitis: HLA, immunoglobulin allotypes and autoantibodies.
Immunogenetic studies of autoimmune chronic active hepatitis: HLA, immunoglobulin allotypes and autoantibodies.
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自身免疫性慢性活动性肝炎的免疫遗传学研究：HLA、免疫球蛋白同种异型和自身抗体。
DOI：
10.1002/hep.1840070621
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
McAuliffe,TL
中科院分区：
文献类型：
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作者：
Krawitt,EL;Kilby,AE;Albertini,RJ;Schanfield,MS;Chastenay,BF;Harper,PC;Mickey,RM;McAuliffe,TL
指定替代表型的策略，定义为对索引病例的无病一级亲属存在抗核和/或抗平滑肌抗体，用于搜索自身免疫性慢性活动性肝炎中假定的疾病易感基因。除检测循环自身抗体状态外，对10例慢性活动性肝炎患者、51例一级亲属和6例配偶进行HLA （A、B和DR位点）和免疫球蛋白等位型（Glm、G2m、G3m和A2m位点）单倍型基因分型。10例慢性活动性肝炎患者中，6例患者HLA单倍型为B8和DR3，其中3例患者还存在免疫球蛋白同种异体单倍型Gm a、x；g.在39%的一级亲属中发现循环自身抗体定义替代表型。然而，分离分析不支持单常染色体显性遗传或隐性遗传的自身抗体阳性表型。一些分析排除了假定的疾病易感位点与HLA（6号染色体）或免疫球蛋白（14号染色体）位点之间的联系。此外，逻辑回归表明，在这些家庭中，免疫遗传标志物与自身抗体均无统计学相关性。因此，尽管自身免疫性慢性活动性肝炎患者的一级亲属中出现自身抗体阳性，但我们没有发现证据表明这一特征具有简单的遗传基础，或者它是慢性活动性肝炎假定疾病易感基因的另一种表现。
The strategy of assigning a surrogate phenotype, defined as the presence of antinuclear and/or antismooth muscle antibodies to disease-free first degree relatives of index cases was used to search for a postulated disease susceptibility gene in autoimmune chronic active hepatitis. In addition to determining circulating autoantibody status, 10 patients, 51 first-degree relatives and 6 spouses of index chronic active hepatitis patients, each ascertained by the single patient, were genotyped for HLA (A, B and DR loci) and immunoglobulin allotype (Glm, G2m, G3m and A2m loci) haplotypes. Among the 10 chronic active hepatitis patients, 6 had HLA haplotypes B8 and DR3, and 3 of these patients had, in addition, the immunoglobulin allotype haplotype Gm a, x; g. Circulating autoantibodies defining the surrogate phenotype was found in 39% of the first-degree relatives. However, segregation analysis offered no support for either single autosomal dominant or recessive inheritance for the autoantibody-positive phenotype. Linkage between the postulated disease susceptibility locus and either the HLA (Chromosome 6) or immunoglobulin (Chromosome 14) locus was excluded by several analyses. Furthermore, logistic regression indicated that neither immunogenetic marker was statistically associated with autoantibody positively in these families. Therefore, despite the occurrence of autoantibody positivity in first-degree relatives of autoimmune chronic active hepatitis patients, we found no evidence that this trait has a simple genetic basis, or that it is an alternative manifestation of a postulated disease susceptibility gene for chronic active hepatitis.