Burch H B, Sellitti D, Barnes S G, Nagy E V, Bahn R S, Burman K D
Endocrine-Metabolic Service, Kyle Metabolic Unit, Walter Reed Army Medical Center, Washington, D.C. 20307-5001.
J Clin Endocrinol Metab. 1994 Jun;78(6):1384-91. doi: 10.1210/jcem.78.6.8200941.
Autoimmunity against the TSH receptor (hTSH-R) is known to be the proximate cause of thyroidal activation in Graves' disease, but has not been definitively linked to extrathyroidal manifestations of this disorder, such as ophthalmopathy and pretibial myxedema. In an effort to increase our knowledge concerning mechanisms responsible for Graves' ophthalmopathy, we used antiserum directed against a highly immunogenic portion of the hTSH-R (amino acids 352-367; P1) to assess the presence of this receptor or immunologically related protein in cultured human retroocular fibroblasts obtained from patients with Graves' ophthalmopathy. Immunoenzymatic and immunofluorescent studies revealed specific staining of both cytoplasmic and cell membrane-associated protein in discrete vesicles. To further evaluate the immunoreactive species present in these cells, immunoblotting experiments were performed using hTSH-R-specific antisera (anti-P1) and sera obtained from patients with Graves' disease. Several protein bands were identified using both anti-P1 and Graves' disease patient sera, including species at mol wt of 95, 71, and 18 kilodaltons, the possible significance of which is discussed. The results support the hypothesis that immunity against the hTSH-R or related proteins contributes to the ophthalmopathy of Graves' disease.
自身免疫性抗促甲状腺激素受体（hTSH-R）是格雷夫斯病中甲状腺激活的直接原因，但尚未明确与该疾病的甲状腺外表现，如眼病和胫前黏液性水肿相关。为了增进我们对格雷夫斯眼病发病机制的了解，我们使用针对hTSH-R高度免疫原性部分（氨基酸352 - 367；P1）的抗血清，来评估从格雷夫斯眼病患者获取的培养人眼后成纤维细胞中该受体或免疫相关蛋白的存在情况。免疫酶法和免疫荧光研究显示，在离散的囊泡中，细胞质和细胞膜相关蛋白均有特异性染色。为进一步评估这些细胞中存在的免疫反应性物质，我们使用hTSH-R特异性抗血清（抗P1）和格雷夫斯病患者血清进行了免疫印迹实验。使用抗P1和格雷夫斯病患者血清均鉴定出了几条蛋白带，包括分子量为95、71和18千道尔顿的条带，并讨论了其可能的意义。结果支持了这样一种假说，即针对hTSH-R或相关蛋白的免疫反应导致了格雷夫斯病的眼病。
