THYROID IMMUNOLOGLOBULINS IN SPORADIC NON-TOXIC GOITER

散发性非毒性甲状腺肿中的甲状腺免疫球蛋白

• 批准号: 3232199
• 负责人: Rosalind Brown
• 金额: $ 10.21万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232199
• 关键词: Graves disease; autoantibody; autoimmune disorder; chromatography; electrofocusing; endocrine disorder diagnosis; glucose 6 phosphate dehydrogenase; goiter; human subject; immunoglobulins; monoclonal antibody; myasthenia gravis; radioassay; radiotracer; thyroid function; thyrotropin; tissue /cell culture

Despite the introduction of iodized salt in the United States in 1924, sporadic nontoxic goiter (NTG) remains one of the most frequent disorders in clinical endocrinology. Recent evidence suggests that thyroid growth in some patients might be due, at least in part, to specific antibodies (thyroid-growth immunoglobulins, TGI) which increases the synthesis by stimulating activity of glucose-6-phosphate dehydrogenase. Immunoglobulins that inhibit (125)I-bTSH binding to thyroid membranes (TSH-binding inhibitory immunoglobulins, TBII can also be detected in some patients and it is not clear whether these reflect the activities of the same or different antibody populations. Likewise it is not known whether TBII & TGI are binding to the high affinity TSH receptor itself or to a neighboring site on the membrane. We propose to elucidate the properties of these autoantibodies and compare them with the TSH receptor autoantibodies that are secreted in excess in Graves' disease. Specifically: 1) we will determine whether TGI and TBII are autoantibodies to the TSH receptor itself. This will be done by determining whether they interact via their F(ab)2 fragments, whether they inhibit (125)I-bTSH binding to solubilized as well as intact thyroid membranes and whether activity is removed by adsorption with membranes enriched in TSH receptor versus control ones. If preliminary studies suggest that they are, we will study more precisely their binding site with the use of (125)I-labeled monoclonal antibodies to the TSH receptor derived from lymphocytes of patients with Graves' disease. 2) We will evaluate whether TGI and TBII are polyclonal or exhibit restricted heterogeneity, characteristic of other receptor antibody-mediated diseases, such as Graves' disease and myasthenia gravis. It is hoped that elucidation of the above properties of TBII and TGI in NTG patients will contribute not only to an understanding of the etiology of NTG, but to current concepts of autoimmune thyroid disease as well. In a longterm sense, information obtained may increase our knowledge of the physiology and pathophysiology of thyroid growth by identifying the site(s) on the membrane which subserve this function.

尽管美国在1924年引入了碘盐， 散发性非毒性甲状腺肿（NTG）仍然是最常见的疾病之一 在临床内分泌学中。 最近的证据表明， 有些患者可能是由于，至少部分， （甲状腺生长免疫球蛋白，TGI），其通过以下方式增加合成： 刺激葡萄糖-6-磷酸脱氢酶的活性。 免疫球 抑制（125）I-bTSH与甲状腺膜结合（TSH结合 抑制性免疫球蛋白，TBII也可以在一些患者中检测到， 不清楚这些是否反映了同一组织的活动， 不同的抗体群体。 同样，也不知道TBII & TGI与高亲和力TSH受体本身或与 膜上的相邻位置。 我们建议阐明这些自身抗体的性质，并比较 他们与TSH受体自身抗体分泌过量， 格雷夫斯病 具体而言：1）我们将确定TGI和TBII是否 是TSH受体自身的抗体 会来做这项工作 确定它们是否通过F（ab）2片段相互作用， 抑制（125）I-bTSH与溶解的以及完整的甲状腺结合 膜以及活性是否通过膜吸附去除 与对照组相比，富含TSH受体。 如果初步研究 我们将更精确地研究它们的结合位点， 使用（125）I标记的TSH受体衍生的单克隆抗体， 从格雷夫斯病患者的淋巴细胞中提取。 2)我们将评估 无论TGI和TBII是多克隆的还是表现出有限的异质性， 其他受体抗体介导的疾病的特征，例如 格雷夫斯病和重症肌无力。 希望通过对NTG中TBII和TGI的上述性质的阐明， 患者不仅有助于了解病因， NTG，但目前的概念，自身免疫性甲状腺疾病以及。 中 从长远来看，获得的信息可能会增加我们对 甲状腺生长的生理学和病理生理学，通过识别部位 在膜上，这有助于这一功能。