Abstract:
Autoantibodies against thyroid proteins are present in several thyroid diseases. Thyroid-stimulating hormone receptor (TSHR) is a G-protein-coupled receptor (GPCR) that binds to thyroid-stimulating hormone (TSH) and stimulates production of thyroxine (T4) and triiodothyronine (T3). When agonized by anti-TSHR autoantibodies, aberrant production of thyroid hormone can lead to Graves\' Disease (GD). In Hashimoto\'s thyroiditis (HT), anti-TSHR autoantibodies target the thyroid for immune attack. To better understand the role of anti-TSHR antibodies in thyroid disease, we generated a set of rat antimouse (m)TSHR monoclonal antibodies with a range of affinities, blocking of TSH, and agonist activity. These antibodies could be used to investigate the etiology and therapy of thyroid disease in mouse models and as building blocks in protein therapeutics that target the thyroid for treatment in either HT or GD.
摘要:
针对甲状腺蛋白的自身抗体存在于几种甲状腺疾病中。促甲状腺激素受体(TSHR)是一种G蛋白偶联受体(GPCR),与促甲状腺激素(TSH)结合并刺激甲状腺素(T4)和三碘甲状腺原氨酸(T3)的产生。当被抗TSHR自身抗体激动时,甲状腺激素的异常产生可导致Graves病(GD)。在桥本甲状腺炎(HT)中,抗TSHR自身抗体靶向甲状腺进行免疫攻击。为了更好地了解抗TSHR抗体在甲状腺疾病中的作用,我们产生了一组具有多种亲和力的大鼠抗小鼠(M)TSHR单克隆抗体,TSH阻断,和激动剂活性。这些抗体可用于研究小鼠模型中甲状腺疾病的病因和治疗,并作为靶向甲状腺的蛋白质疗法的基础,用于HT或GD中的治疗。