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利用合成肽检测格雷夫斯病患者针对促甲状腺素受体的细胞和抗体反应的异质性。

Heterogeneity in cellular and antibody responses against thyrotropin receptor in patients with Graves' disease detected using synthetic peptides.

作者信息

Fan J L, Desai R K, Seetharamaiah G S, Dallas J S, Wagle N M, Prabhakar B S

机构信息

Department of Microbiology, University of Texas Medical Branch at Galveston 77555.

出版信息

J Autoimmun. 1993 Dec;6(6):799-808. doi: 10.1006/jaut.1993.1065.

DOI:10.1006/jaut.1993.1065
PMID:7512341
Abstract

Graves' disease (GD) is characterized by the presence of autoantibodies to the thyrotropin receptor (TSHr). These antibodies bind to the TSHr and stimulate thyroid cells, thus causing hyperthyroidism. To understand the regulation of TSHr-specific immune responses in Graves' disease, it is important to evaluate the T-cell response in patients with GD against TSHr. In this study we used 11 different peptides that were derived from two regions (i.e. amino acid, AA 12-46 and 316-397) unique to the TSHr when compared to other glycoprotein hormone receptors, and which also have the highest predicted immunogenicity. We evaluated both lymphocyte proliferation as a measure of T-cell response and antibody binding to each of these peptides in nine patients with GD and eight healthy subjects. Patients with GD showed considerable lymphocyte proliferative and antibody responses against several of these peptides. There was considerable heterogeneity in immune responses amongst the patients. Moreover, our data suggested that several peptides contained both T cell and antibody reactive epitopes and might represent some of the highly immunogenic regions of the TSHr.

摘要

格雷夫斯病(GD)的特征是存在促甲状腺激素受体(TSHr)自身抗体。这些抗体与TSHr结合并刺激甲状腺细胞,从而导致甲状腺功能亢进。为了解格雷夫斯病中TSHr特异性免疫反应的调节,评估GD患者针对TSHr的T细胞反应很重要。在本研究中,我们使用了11种不同的肽,这些肽源自TSHr与其他糖蛋白激素受体相比特有的两个区域(即氨基酸,AA 12 - 46和316 - 397),并且还具有最高的预测免疫原性。我们评估了9例GD患者和8名健康受试者的淋巴细胞增殖作为T细胞反应的指标,以及抗体与这些肽中每一种的结合情况。GD患者对其中几种肽表现出相当程度的淋巴细胞增殖和抗体反应。患者之间的免疫反应存在相当大的异质性。此外,我们的数据表明,几种肽同时包含T细胞和抗体反应性表位,可能代表了TSHr的一些高免疫原性区域。

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Heterogeneity in cellular and antibody responses against thyrotropin receptor in patients with Graves' disease detected using synthetic peptides.利用合成肽检测格雷夫斯病患者针对促甲状腺素受体的细胞和抗体反应的异质性。
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引用本文的文献

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Biased signaling by thyroid-stimulating hormone receptor-specific antibodies determines thyrocyte survival in autoimmunity.甲状腺刺激素受体特异性抗体的信号偏向决定了自身免疫中甲状腺细胞的存活。
Sci Signal. 2018 Jan 23;11(514):eaah4120. doi: 10.1126/scisignal.aah4120.
2
How one TSH receptor antibody induces thyrocyte proliferation while another induces apoptosis.一种促甲状腺激素受体抗体如何诱导甲状腺细胞增殖,而另一种却诱导其凋亡。
J Autoimmun. 2013 Dec;47:17-24. doi: 10.1016/j.jaut.2013.07.009. Epub 2013 Aug 17.