Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.
J Clin Endocrinol Metab. 2011 Aug;96(8):2386-94. doi: 10.1210/jc.2011-0307. Epub 2011 Jun 15.
The immunopathogenesis of Graves' ophthalmopathy (GO) is still incompletely understood. Attention has shifted from the TSH receptor (TSHR) to the IGF-I receptor (IGF-1R) as a major autoantigen. This review on the pathophysiology of GO focused on orbital fibroblasts and the question whether autoimmunity against TSHR or IGF-1R is primarily involved.
Relevant papers on GO were identified by a search on PubMed and scrutiny of their reference lists. In addition, abstracts presented on GO at the 14th International Thyroid Congress in 2010 in Paris, France, were read.
Orbital fibroblasts (OF) are recognized as the prime target cells of the autoimmune attack in GO. In early stages OF are undifferentiated with low TSHR expression and are stimulated to produce hyaluronan by cytokines (released by activated infiltrating T cells) and not by Graves' IgG. OF lacking the surface glycoprotein Thy-1 (not present in the muscle compartment) may differentiate into adipocytes, associated with increased TSHR expression. Graves IgG stimulate hyaluronan in differentiated OF mostly via non-cAMP signaling pathways for growth, which can also be activated via TSHR. The existence of IGF-1R stimulating antibodies in serum remains dubious. Autoimmunity against IGF-1R is also observed in rheumatoid arthritis and is not specific for Graves' disease. Expression of IGF-1R on T and B lymphocytes may contribute to autoimmunity against fibroblasts.
Autoimmunity against TSHR is most likely initiating the immune response in GO. Autoimmunity against IGF-1R is not specific for Graves' DISEASE but may contribute to ongoing immune reactions.
格雷夫斯眼病（GO）的免疫发病机制仍不完全清楚。人们的注意力已经从促甲状腺激素受体（TSHR）转移到胰岛素样生长因子-I 受体（IGF-1R），认为它是主要的自身抗原。这篇关于 GO 病理生理学的综述重点关注眼眶成纤维细胞，并提出了一个问题，即针对 TSHR 或 IGF-1R 的自身免疫反应是否是主要的参与因素。
通过在 PubMed 上搜索并仔细查阅其参考文献，确定了与 GO 相关的论文。此外，还阅读了在 2010 年法国巴黎举行的第 14 届国际甲状腺大会上关于 GO 的摘要。
眼眶成纤维细胞（OF）被认为是 GO 中自身免疫攻击的主要靶细胞。在早期，OF 是未分化的，TSHR 表达水平较低，它们受到细胞因子（由激活的浸润 T 细胞释放）的刺激产生透明质酸，而不是 Graves 免疫球蛋白。缺乏表面糖蛋白 Thy-1（肌肉组织中不存在）的 OF 可能分化为脂肪细胞，同时 TSHR 表达增加。Graves 免疫球蛋白通过非 cAMP 信号通路刺激分化的 OF 产生透明质酸，主要用于生长，也可以通过 TSHR 激活。血清中存在 IGF-1R 刺激抗体的说法仍存在争议。针对 IGF-1R 的自身免疫也在类风湿关节炎中观察到，并且不是 Graves 病所特有的。T 和 B 淋巴细胞上 IGF-1R 的表达可能有助于针对成纤维细胞的自身免疫。
针对 TSHR 的自身免疫反应很可能是 GO 中免疫反应的起始因素。针对 IGF-1R 的自身免疫反应不是 Graves 病所特有的，但可能有助于持续的免疫反应。
