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: 3152953
• 负责人: Rosalind Brown
• 金额: $ 11.03万
• 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/3152953
• 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1924年美国引入了加碘盐，

项目成果

Further studies on thyroid growth-stimulating immunoglobulins in euthyroid nonendemic goiter.

甲状腺功能正常的非地方性甲状腺肿中甲状腺生长刺激免疫球蛋白的进一步研究。

• DOI: 10.1210/jcem-60-5-972
• 发表时间: 1985
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: vanderGaag,RD;Drexhage,HA;Wiersinga,WM;Brown,RS;Docter,R;Bottazzo,GF;Doniach,D
• 通讯作者: Doniach,D