ETHNIC VARIATION AND AUTOIMMUNITY

易患多种疾病，疑似自身免疫性 起源，与免疫球蛋白超基因家族的基因有关。 这些基因包括主要的II类基因， 组织相容性复合物，免疫球蛋白基因，以及 编码T淋巴细胞上的抗原特异性受体。 我们将 研究三种疾病，包括重症肌无力和天疱疮， 寻常，这是自身免疫性疾病介导的明显例子， 和多发性硬化症，一种假定的自身免疫性疾病， 神经系统疾病 我们将研究MHC类之间的关联 II基因、免疫球蛋白基因和TcR基因与这些疾病 使用RFLP分析和基因组测序，利用 聚合酶链反应技术。 我们看到 II类HLA基因、免疫球蛋白重链 同种异型和T细胞受体基因型和易感性 通常在患有这些疾病的个体中维持 不同的种族背景。 这些数据提供了有力的支持 这些基因直接参与自身免疫性疾病， 因为与易感性相关的等位基因不太可能 在不同种族中与相同的等位基因保持连锁 边界 我们将研究北卡罗来纳州的MS、MG和PV患者， 美国、日本、澳大利亚、法国、奥地利和以色列（阿拉伯和 犹太人）。 免疫球蛋白超基因和 为了设计新的治疗方法， 从人类自身免疫性疾病的方法， 治疗实验室动物的自身免疫性疾病， 恒河猴

Susceptibility to many diseases, suspected to be of autoimmune origin, is linked to genes of the immunoglobulin supergene family. These genes include the class II genes of the major histocompatibility complex, the immunoglobulin genes, and the genes encoding the antigen-specific receptor on T lymphocytes. We will study three diseases, including myasthenia gravis and pemphigus vulgaris, that are clear examples of autoimmune conditions mediated by antibody, and multiple sclerosis, a putative autoimmune neurologic disease. We will study associations between MHC class II genes, immunoglobulin genes, and TcR genes and these diseases using RFLP analysis and genomic sequencing, utilizing the polymerase chain reaction technology. We have seen that associations between class II HLA genes, immunoglobulin heavy chain allotype and T cell receptor genotype and susceptibility to disease, are often maintained in individuals with these diseases of different ethnic backgrounds. These data provide strong support for a direct participation for these genes in autoimmune disease, since it is unlikely that an allele linked to susceptibility would have remained in linkage with the same alleles across ethnic boundaries. We will study patients with MS, MG and PV in North America, Japan, Australia, France, Austria, and Israel (Arab and Jew). These associations between immunoglobulin supergenes and disease have been exploited in order to design new therapeutic approaches from human autoimmune disease that have shown results in treating autoimmune conditions in laboratory animals including rhesus monkeys.