IMMUNOTOXIC EFFECTS OF IODINE

通过饮食或治疗增加环境中的碘暴露 来源可能是自身免疫发病率不断上升的原因之一 人类的甲状腺炎。高碘甲状腺球蛋白，660kD 糖蛋白是甲状腺激素的主要存储形式，由于增加 碘的摄入与发病率和严重程度的增加有关 在鸡的自发性自身免疫性甲状腺炎和糖尿病中- 易感淋巴细胞性甲状腺炎相关BB/W大鼠。临床观察 人类也认为过量的碘是自身免疫的增强剂 甲状腺疾病，但没有关于其发病机制的实验信息 在人类身上是可用的。碘在多因素研究中的作用 自身免疫性疾病，如慢性淋巴细胞性甲状腺炎，是 过于频繁地被忽视，这可能解释了许多 不同人群自身免疫性甲状腺疾病发病率的差异 地理区域。我们建议探索在免疫方面的差异 甲状腺球蛋白及其片段对不同程度碘化的反应 自身免疫性甲状腺疾病患者与 有甲状腺自身抗体的甲状腺功能正常的个体。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。胰酶- 高效液相解析的消化多肽图谱将使我们能够比较模式 不同的TG制剂中的碘化程度。第二，我们建议， 评价不同碘化程度的细胞免疫反应 甲状腺球蛋白或其碎片。人类的功能反应 淋巴细胞对不同碘甲状腺球蛋白及其片段的影响 通过细胞增殖试验进行检测。我们将开发一种 一系列T细胞系/克隆来测试T细胞的优良特性 细胞反应。然后我们将研究细胞的标记 增殖(如IL-2、IL-4分泌)以确定特定阶段 甲状腺球蛋白或其碎片在其中发挥作用。这个 最终目标是了解碘在人体内的免疫毒性作用 诱发自身免疫性甲状腺疾病希望发展起来 预防策略。

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.