Winchester Robert
Division of Autoimmune and Molecular Diseases, Departments of Pediatrics and Medicine, Columbia University, School of Medicine, 630 West 168th Street, PH4-477, New York, NY 10032, USA.
Rheum Dis Clin North Am. 2004 Feb;30(1):213-27, viii. doi: 10.1016/S0889-857X(03)00112-1.
This article emphasizes the interpretation of the meaning and significance of the genetic aspects of susceptibility to certain autoimmune-mediated rheumatic diseases. The familial aggregation and identical twin concordance that provides the basis of considering these as genetic diseases are reviewed. Major histocompatibility complex (MHC) genes are taken as the primary examples of candidate genes that regulate the immune response; the potential function of these genes in predisposing to autoimmune diseases is analyzed. Autoimmune diseases are discussed as the consequence of the role of MHC molecules encoded by different alleles that exhibit distinct peptide-binding properties and select a self reactive T-cell repertoire. The low penetrance rates of autoimmune-mediated rheumatic disease is used as an argument that stochastic events in the generation and postthymic maturation of the somatically expressed T-cell repertoire account for the characteristically delayed onset of these diseases. The importance of self-reactivity in the physiologic immune response is used as an argument that the events that are responsible for the development of an autoimmune disease are an untoward exaggeration of normal immune responsiveness, but not a qualitatively distinct biologic event.
本文着重阐述了某些自身免疫介导的风湿性疾病易感性的遗传因素的意义及重要性。文中回顾了将这些疾病视为遗传性疾病的家族聚集性和同卵双胞胎一致性。主要组织相容性复合体（MHC）基因被作为调节免疫反应的候选基因的主要例子；分析了这些基因在自身免疫性疾病易感性方面的潜在功能。自身免疫性疾病被视为由不同等位基因编码的MHC分子的作用导致的结果，这些等位基因具有不同的肽结合特性，并选择了自身反应性T细胞库。自身免疫介导的风湿性疾病的低外显率被用作一个论据，即体细胞表达的T细胞库在生成和胸腺后成熟过程中的随机事件导致了这些疾病典型的延迟发病。自身反应性在生理性免疫反应中的重要性被用作一个论据，即导致自身免疫性疾病发生的事件是正常免疫反应的不良过度，而不是性质上不同的生物学事件。
