PATHOGENESIS AND THERAPY OF AUTOIMMUNE THYROID DISEASE

将进行研究，以确定基本的异常， 免疫系统的功能导致甲状腺自身免疫， Graves病、甲状腺炎和特发性甲状腺炎的临床疾病综合征 粘液水肿 甲状腺微粒体抗原将溶解，纯化， 免疫吸收或免疫沉淀，通过电泳分离，和 通过Western Blotting鉴定。 细胞表面和膜蛋白将被 碘化或用35S甲硫氨酸标记。 蛋白质将通过 电泳和抗原将通过蛋白质印迹检测。 初步 研究表明不同的血清识别不同的抗原表位 在非变性、变性或还原和变性条件下。 我们 将抗体反应模式的类型与临床特征联系起来 疾病。 初步数据表明微粒体抗原 与甲状腺过氧化物酶密切相关，各种研究将 为了证明或反驳这种可能性而追求。 我们会发现 微粒体抗原上的不同表位，使用溴化氰或 抗原的蛋白酶V8片段化和蛋白质印迹或柱 技术. 将尝试鉴定特异性抗原， AITD患者最常接种的疫苗。 为了研究反馈控制系统的调节功能， 微粒体抗体的产生，我们将寻找微粒体抗原， 血清，并将开发识别抗独特型抗体的方法 针对微粒体抗体表位。 T细胞反应性 微粒体抗原将使用外周血淋巴细胞进行表征。 血液甲状腺组织或颈部淋巴结 T细胞克隆将是 使用软琼脂培养或试管孵育系统开发。 的T 细胞系将用于控制B细胞功能的研究， 与自体甲状腺细胞的体外反应性。 如果有足够的时间 我们将尝试克隆微粒体抗原的基因， 评估基因结构或表达的差异。

Research will be conducted in an effort to establish basic abnormalities in the function of the immune system leading to thyroid autoimmunity and the clinical disease syndromes of Graves' disease, thyroiditis, and idiopathic myxedema. Thyroid microsomal antigen will be solubilized, purified by immunoabsorption or immunoprecipitation, separated by electrophoresis, and identified by Western Blotting. Cell surface and membrane proteins will be iodinated or labeled with 35S methionine. Proteins will be separated by electrophoresis and antigens will be detected by Western Blot. Preliminary studies have shown that different sera recognize different antigen epitopes in non-denaturing, denaturing, or reduced and denaturing conditions. We will relate the type of antibody reaction pattern to the clinical features of the disease. Preliminary data has suggested that the microsomal antigen is closely related to thyroid peroxidase, and a variety of studies will be pursued in order to prove or disprove this possibility. We will detect different epitopes on the microsomal antigen using cyanogen bromide or protease V8 fragmentation of the antigen and Western blotting or column techniques. An attempt will be made to identify the specific antigens to which patients with AITD most frequently are immunized. In order to study function of the feedback control system regulating microsomal antibody production, we will look for microsomal antigen in serum, and will develop methods for recognizing anti-idiotype antibodies directed against microsomal antibody epitopes. T cell reactivity to microsomal antigen will be characterized using lymphocytes from peripheral blood, thyroid tissue, or neck lymph nodes. T cell clones will be developed using a soft agar culture or test tube incubation system. The T cell lines will be used in studies of control of B cell function and in vitro reactivity with autologous thyroid cells. If sufficient time is available, we will attempt to clone the gene for the microsomal antigen and assess differences in structure or expression of the gene.