Novel Antimurine Thyroid-Stimulating Hormone Receptor Monoclonal Antibodies.

Alyssa N Klee, James A Torchia, Gordon J Freeman
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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.

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新型抗嘌呤甲状腺刺激素受体单克隆抗体
多种甲状腺疾病都存在针对甲状腺蛋白的自身抗体。促甲状腺激素受体(TSHR)是一种G蛋白偶联受体(GPCR),能与促甲状腺激素(TSH)结合,刺激甲状腺素(T4)和三碘甲状腺原氨酸(T3)的产生。当抗 TSHR 自身抗体激动时,甲状腺激素的异常分泌会导致巴塞杜氏病(GD)。在桥本氏甲状腺炎(HT)中,抗TSHR自身抗体会攻击甲状腺。为了更好地了解抗TSHR抗体在甲状腺疾病中的作用,我们生成了一组大鼠抗小鼠(m)TSHR单克隆抗体,它们具有不同的亲和力、TSH阻断能力和激动活性。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,也可作为蛋白质疗法的基石,靶向治疗甲状腺功能亢进症或甲状腺功能减退症。
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CiteScore
4.80
自引率
0.00%
发文量
49
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