THYROID IMMUNOLOGLOBULINS IN SPORADIC NON-TOXIC GOITER

尽管美国在1924年引入了加碘盐， 散发性非毒性甲状腺肿(NTG)仍然是最常见的疾病之一。 临床内分泌学。最近的证据表明，甲状腺的生长 一些患者可能至少部分是由于特定的抗体所致。 (甲状腺生长免疫球蛋白，TGI)，通过以下方式增加合成 刺激葡萄糖-6-磷酸脱氢酶的活性。免疫球蛋白 抑制(125)I-bTSH与甲状腺膜的结合(TSH结合 抑制性免疫球蛋白，TBII也可以在一些患者和 目前尚不清楚这些活动是否反映了同样的或 不同的抗体群。同样，目前还不知道TBII和 TGI与高亲和力TSH受体本身或与 膜上邻近的位置。 我们建议阐明这些自身抗体的特性并比较 它们携带的TSH受体自身抗体在体内分泌过多 格雷夫斯病。具体：1)我们将确定TGI和TBII 是针对促甲状腺激素受体本身的自身抗体。这将通过以下方式完成 确定它们是否通过其F(Ab)2片段相互作用，是否它们 抑制(125)I-bTSH与溶解的和完整的甲状腺的结合 膜和活性是否通过与膜的吸附来去除 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部位 ~(125)I标记的抗TSH受体单抗的应用 从Graves病患者的淋巴细胞中提取。2)我们将进行评估 无论TGI和TbII是多克隆的还是表现出受限的异质性， 其他受体抗体介导的疾病的特征，如 格雷夫斯病和重症肌无力。 希望阐明NTG中TBII和TGI的上述性质 患者不仅将有助于了解本病的病因 NTG，但也适用于目前的自身免疫性甲状腺疾病的概念。在一个 从长期意义上讲，获得的信息可能会增加我们对 甲状腺生长的定位生理学和病理生理学(S) 在辅助这一功能的膜上。

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.