IMMUNOTOXIC EFFECTS OF IODINE

碘的免疫毒性作用

• 批准号: 2142157
• 负责人: Carol Lynne Burek
• 金额: $ 11.6万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2142157
• 关键词: IMMUNOTOXIC; EFFECTS; IODINE

Increased environmental exposure to iodine from dietary or therapeutic sources may contribute to the escalating prevalence of autoimmune thyroiditis in humans. Highly iodinated thyroglobulin, the 660 Kd glycoprotein major storage form of thyroid hormones, due to increased iodine intake, has been associated with increased incidence and severity of spontaneous autoimmune thyroiditis in chickens and in the diabetes- prone lymphocytic thyroiditis-associated BB/W rat. Clinical observations in humans also associate excess iodine as a potentiator of autoimmune thyroid disease, but no experimental information about the pathogenesis in humans is available. The role of iodine in a multifactorial autoimmune disease like chronic lymphocytic thyroiditis is a factor that has too frequently been neglected and may account for many of the differences in frequency of autoimmune thyroid disease among geographical areas. We propose to explore the differences in the immune response to thyroglobulin and its fragments iodinated to varying degrees between patients suffering from autoimmune thyroid disease compared to euthyroid individuals with thyroid autoantibodies. First, studies will concentrate on the preparation, iodination, isolation, and identification of the relevant thyroglobulin and its fragments. Tryptic- digest peptide maps resolved by HPLC will enable us to compare patterns of iodination among the various Tg preparations. Second, we propose, to evaluate cellular human immune response to variously iodinated thyroglobulin or its fragments. The functional responses of human lymphocytes to variously iodinated thyroglobulin and its fragments will be tested by means of cell proliferation assays. We will develop a series of T cell lines/clones to test the fine specificities of the cellular response. We will then investigate markers of cellular proliferation (e.g. IL-2, IL-4 secretion) to pinpoint the specific stage at which the thyroglobulin or its fragments is playing a role. The ultimate goal is to understand the immunotoxic role of iodine in inducing autoimmune thyroid disease with the hope of developing preventive strategies.

通过饮食或治疗增加环境中碘暴露 来源可能导致自身免疫性疾病的患病率不断上升， 人类的甲状腺炎高碘甲状腺球蛋白，660 Kd 糖蛋白主要储存形式的甲状腺激素，由于增加 碘摄入量与发病率和严重程度增加有关 鸡和糖尿病患者的自发性自身免疫性甲状腺炎 易感淋巴细胞性甲状腺炎相关BB/W大鼠。临床观察结果 在人类中，过量碘也是自身免疫增强剂 甲状腺疾病，但没有关于发病机制的实验信息 在人类中是可用的。碘在多因素 自身免疫性疾病如慢性淋巴细胞性甲状腺炎是一个因素， 经常被忽视，这可能是造成许多问题的原因 自身免疫性甲状腺疾病的发生率差异 地理区域。我们建议探索免疫系统的差异， 对甲状腺球蛋白及其碎片碘化程度不同的反应 自身免疫性甲状腺疾病患者与 甲状腺自身抗体的甲状腺功能正常个体。首先，研究将 专注于制备、碘化、分离和 相关甲状腺球蛋白及其片段的鉴定。胰蛋白酶- 通过HPLC解析的消化肽图谱将使我们能够比较模式 不同Tg制剂间碘化的差异。第二，我们建议， 评价细胞对各种碘化的人体免疫应答 甲状腺球蛋白或其片段。人类的功能反应 淋巴细胞对各种碘化甲状腺球蛋白及其碎片的反应， 通过细胞增殖试验进行检测。我们将开发一个 一系列的T细胞系/克隆，以测试细胞的精细特异性。 细胞反应。然后我们将研究细胞标记物， 增殖（例如IL-2、IL-4分泌），以确定特定阶段 甲状腺球蛋白或其片段在其中发挥作用。的 最终目标是了解碘在免疫系统中的作用。 诱发自身免疫性甲状腺疾病 预防战略。