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促甲状腺激素受体研究的最新进展与“自身免疫性促甲状腺激素受体疾病”的新概念

Recent progress in TSH receptor studies with a new concept of "autoimmune TSH receptor disease".

作者信息

Mori T, Akamizu T, Kosugi S, Sugawa H, Inoue D, Okuda J, Ueda Y

机构信息

Department of Laboratory Medicine, Kyoto University School of Medicine, Japan.

出版信息

Endocr J. 1994 Feb;41(1):1-11. doi: 10.1507/endocrj.41.1.

DOI:10.1507/endocrj.41.1
PMID:7524929
Abstract

Recent progress in the studies of epitope analysis of the TSH-R against TSH-R Ab was reviewed extensively. Using both site-directed mutagenesis and synthetic TSH-R peptide, binding and/or action sites of TSH-R Ab have been known to be multiple and discontinuous, but the significance of two unique and TSH-R specific regions has been implicated. Further, the possible existence of heterogeneity among stimulatory TSH-R Ab has also been indicated. As for immunogenetic factors related to autoimmune thyroid diseases, studies on HLA analysis, TSH-R specific T lymphocyte analysis and VH analysis of TSH-R Ab were discussed. Of note was the negative association of HLA-DP w2 antigen in Japanese patients with Graves' disease and hypothyroidism due to blocking TSH-R Ab, and we proposed a new concept of autoimmune TSH receptor disease within autoimmune thyroid disease and emphasized possible critical roles of HLA-DP. Recent evidence of restricted usage of the Ig VH gene in cloned B lymphocytes from Graves' patients producing TSH-R Ab has also been presented.

摘要

广泛综述了促甲状腺激素受体(TSH-R)针对促甲状腺激素受体抗体(TSH-R Ab)的表位分析研究的最新进展。利用定点诱变和合成TSH-R肽,已知TSH-R Ab的结合和/或作用位点是多个且不连续的,但两个独特的TSH-R特异性区域的意义已被提及。此外,还指出了刺激性TSH-R Ab之间可能存在异质性。关于自身免疫性甲状腺疾病相关的免疫遗传因素,讨论了HLA分析、TSH-R特异性T淋巴细胞分析以及TSH-R Ab的VH分析。值得注意的是,在日本格雷夫斯病患者和因阻断TSH-R Ab导致的甲状腺功能减退患者中,HLA-DP w2抗原呈负相关,我们提出了自身免疫性甲状腺疾病中自身免疫性促甲状腺激素受体疾病的新概念,并强调了HLA-DP可能的关键作用。还展示了来自产生TSH-R Ab的格雷夫斯病患者的克隆B淋巴细胞中Ig VH基因限制性使用的最新证据。

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Recent progress in TSH receptor studies with a new concept of "autoimmune TSH receptor disease".促甲状腺激素受体研究的最新进展与“自身免疫性促甲状腺激素受体疾病”的新概念
Endocr J. 1994 Feb;41(1):1-11. doi: 10.1507/endocrj.41.1.
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Use of cells expressing the human thyrotropin (TSH) receptor for the measurement of thyroid stimulating and TSH-blocking antibodies.使用表达人促甲状腺激素(TSH)受体的细胞来测量促甲状腺抗体和TSH阻断抗体。
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Antibodies to TSH-receptor in thyroid autoimmune disease interact with monoclonal antibodies whose epitopes are broadly distributed on the receptor.甲状腺自身免疫性疾病中针对促甲状腺激素受体的抗体与表位广泛分布于该受体上的单克隆抗体相互作用。
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[Anti-thyrotropin (TSH) receptor antibody binding epitopes of TSH receptor: site-directed mutagenesis approach].[促甲状腺激素(TSH)受体的抗促甲状腺激素(TSH)受体抗体结合表位:定点诱变方法]
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Thyrotropin receptor T cell epitopes in autoimmune thyroid disease.自身免疫性甲状腺疾病中的促甲状腺激素受体T细胞表位
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Evaluating the role of Th0 and Th1 clones in autoimmune thyroid disease by use of Hu-SCID chimeras.利用人-严重联合免疫缺陷(Hu-SCID)嵌合体评估Th0和Th1克隆在自身免疫性甲状腺疾病中的作用。
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Identification of separate determinants on the thyrotropin receptor reactive with Graves' thyroid-stimulating antibodies and with thyroid-stimulating blocking antibodies in idiopathic myxedema: these determinants have no homologous sequence on gonadotropin receptors.在特发性黏液性水肿中鉴定促甲状腺素受体上与格雷夫斯病促甲状腺素刺激抗体和促甲状腺素阻断抗体反应的不同决定簇:这些决定簇在促性腺激素受体上没有同源序列。
Mol Endocrinol. 1992 Feb;6(2):168-80. doi: 10.1210/mend.6.2.1349156.

引用本文的文献

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Thyroid-stimulating antibody and TSH-binding inhibitor immunoglobulin in 277 Graves' patients and in 686 normal subjects.277例格雷夫斯病患者及686名正常受试者体内的促甲状腺素抗体和促甲状腺素结合抑制性免疫球蛋白
J Endocrinol Invest. 1997 Sep;20(8):452-61. doi: 10.1007/BF03348001.
2
Statistical analysis of functional region(s) of the TSH receptor.促甲状腺激素受体功能区的统计分析
J Endocrinol Invest. 1995 Oct;18(9):710-7. doi: 10.1007/BF03349793.