Murakami M, Mori M
Department of Internal Medicine, Gunma University, School of Medicine, Maebashi.
Rinsho Byori. 1993 Feb;41(2):128-35.
Immunogenic regions in human TSH receptors responsible for autoimmune thyroid disease were studied using synthetic TSH receptor-related peptides. Eight different peptides corresponding to segments of the extracellular domain of TSH receptor were synthesized. Immunoglobulin G(IgG) of patients with Graves' disease bound to two of eight peptides, peptide # 1 (32-56) and peptide # 5(309-337). IgG of patients with Hashimoto's thyroiditis bound to a different region of TSH receptors, peptide #8 (333-359). One of three rabbit antisera against peptide #1 showed significant thyroid stimulating activity, although rabbit antisera against peptide #5 lacked the stimulating activity. An antiserum against peptide #1, but none of those one against peptide #5, recognized TSH receptor-like immunoreactivity in human peripheral blood. The molecular weight of the immunoreactivity was approximately 60kDa, on both high performance gel filtration chromatography and Western blot analysis. The amount of peptide #1 immunoreactivity was significantly higher in Graves' plasma than that in plasma of either normal or hypothyroid patients with Hashimoto's thyroiditis. These results indicate that the main immunogenic region for Graves' IgG exists near the N-terminal of human TSH receptors and TSH receptor-like immunoreactivity is present in human peripheral blood, which may contribute to the pathophysiology of Graves' disease.
利用合成的促甲状腺激素（TSH）受体相关肽段，研究了人类TSH受体中与自身免疫性甲状腺疾病相关的免疫原性区域。合成了与TSH受体细胞外结构域片段相对应的8种不同肽段。格雷夫斯病患者的免疫球蛋白G（IgG）与8种肽段中的两种结合，即肽段#1（32 - 56）和肽段#5（309 - 337）。桥本甲状腺炎患者的IgG与TSH受体的不同区域结合，即肽段#8（333 - 359）。三种针对肽段#1的兔抗血清中有一种显示出显著的甲状腺刺激活性，而针对肽段#5的兔抗血清则缺乏这种刺激活性。一种针对肽段#1的抗血清能识别出人类外周血中的TSH受体样免疫反应性，而针对肽段#5的抗血清则不能。在高效凝胶过滤色谱和蛋白质印迹分析中，这种免疫反应性的分子量约为60kDa。格雷夫斯病患者血浆中肽段#1免疫反应性的量显著高于正常或患有桥本甲状腺炎的甲状腺功能减退患者血浆中的量。这些结果表明，格雷夫斯病IgG的主要免疫原性区域存在于人类TSH受体的N端附近，且人类外周血中存在TSH受体样免疫反应性，这可能与格雷夫斯病的病理生理学有关。
