Huang D, Liu L, Norén K, Xia S Q, Trifunovic J, Pirskanen R, Lefvert A K
Immunological Research Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
J Neuroimmunol. 1998 Aug 1;88(1-2):192-8. doi: 10.1016/s0165-5728(98)00119-2.
Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) plays a pivotal role in downregulating both the cellular and the humoral response by suppressing ongoing responses of activated T cells. Our earlier study showed that genetic variations in interleukin-1 genes confer susceptibility to myasthenia gravis, especially in patients having the lowest risk from major histocompatibility complex genes. Here we describe an association of Ctla-4 gene to the disease with thymoma and a higher prevalence of CTLA-4 gene polymorphism allele 104 in patients positive for IL-1beta TaqI allele 2, an IL-1beta 'high secretor' phenotype. There was no association in patients with hyperplasia and normal thymic histology. These results further advocate that MG is a polygenetic disease and suggest that co-stimulators such as CTLA-4 and CD28 might have an important role in the pathogenesis of the disease.
细胞毒性T淋巴细胞相关抗原4（CTLA-4）通过抑制活化T细胞的持续反应，在下调细胞免疫和体液免疫反应中起关键作用。我们早期的研究表明，白细胞介素-1基因的遗传变异赋予重症肌无力易感性，尤其是在主要组织相容性复合体基因风险最低的患者中。在此，我们描述了Ctla-4基因与伴有胸腺瘤的该疾病的关联，以及IL-1βTaqI等位基因2（一种IL-1β“高分泌者”表型）阳性患者中CTLA-4基因多态性等位基因104的较高患病率。增生和胸腺组织学正常的患者中无此关联。这些结果进一步支持重症肌无力是一种多基因疾病，并提示共刺激分子如CTLA-4和CD28可能在该疾病的发病机制中起重要作用。
