HLA - DRB1基因多态性决定转基因小鼠对自身免疫性甲状腺炎的易感性：与HLA - DRB1*0301（DR3）基因存在明确关联。
HLA-DRB1 polymorphism determines susceptibility to autoimmune thyroiditis in transgenic mice: definitive association with HLA-DRB1*0301 (DR3) gene.
作者信息
Kong Y C, Lomo L C, Motte R W, Giraldo A A, Baisch J, Strauss G, Hämmerling G J, David C S
机构信息
Department of Immunology and Microbiology, Wayne State University, Detroit, Michigan 48201, USA.
出版信息
J Exp Med. 1996 Sep 1;184(3):1167-72. doi: 10.1084/jem.184.3.1167.
Abstract
Familial clustering of autoimmune thyroid diseases has led to studies of their association with human major histocompatibility complex (MHC) class II genes. One such gene implicated in Hashimoto's thyroiditis (HT) is HLA-DR3, but the association is weak and is contradicted by other reports. On the other hand, murine experimental autoimmune thyroiditis (EAT), a model for HT, presents a clear linkage with MHC class II. Moreover, it is inducible with thyroglobulin (Tg), the common autoantigen in either species. Immunization of HLA-DRB1* 0301 (DR3) transgenic mice with mouse or human Tg resulted in severe thyroiditis. In contrast, transgenic mice expressing the HLA-DRB1*1502 (DR2) gene were resistant to EAT. Our studies show that HLA-DRB1 polymorphism determines susceptibility to autoimmune thyroiditis and implicate Tg as an important autoantigen.
摘要
自身免疫性甲状腺疾病的家族聚集现象促使人们对其与人类主要组织相容性复合体（MHC）II类基因的关联进行研究。一个与桥本甲状腺炎（HT）相关的此类基因是HLA - DR3，但这种关联较弱，且与其他报告相矛盾。另一方面，小鼠实验性自身免疫性甲状腺炎（EAT），一种HT的模型，与MHC II类呈现出明确的连锁关系。此外，它可由甲状腺球蛋白（Tg）诱导产生，Tg是这两个物种中的共同自身抗原。用小鼠或人Tg免疫HLA - DRB10301（DR3）转基因小鼠会导致严重的甲状腺炎。相比之下，表达HLA - DRB11502（DR2）基因的转基因小鼠对EAT具有抗性。我们的研究表明，HLA - DRB1多态性决定了对自身免疫性甲状腺炎的易感性，并表明Tg是一种重要的自身抗原。
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