Immunopathogenesis of thyroid eye disease: emerging paradigms.
Immunopathogenesis of thyroid eye disease: emerging paradigms.
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DOI：
10.1016/j.survophthal.2009.06.009
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发表时间：
2010-05
影响因子：
5.1
通讯作者：
Douglas RS
中科院分区：
文献类型：
--
作者：
Naik VM;Naik MN;Goldberg RA;Smith TJ;Douglas RS
Graves病是一种全身性自身免疫过程，靶向甲状腺、眼眶和胫前皮肤。甲状腺功能障碍是可以治疗的，但还没有持续有效的药物治疗Graves病的眼眶表现，也称为甲状腺相关眼病或甲状腺眼病。几种自身抗原可能与甲状腺眼病的发病机制有关。在大多数患者中可以检测到针对促甲状腺激素受体产生的激活抗体，这些抗体驱动甲状腺功能亢进症。然而，刺激性抗胰岛素样生长因子-1受体（IGF-1 R）抗体也可能在GD的甲状腺外表现中发挥作用。IGF-1 R在TED患者眼眶成纤维细胞中过度表达，而IGF-1 R + T和IGF-1 R + B细胞在GD中更为常见。在甲状腺眼病中，几种细胞因子的作用和眼眶特有的分子相互作用似乎引起炎症、脂肪扩张和过量细胞外基质分子的沉积。基于这些新的见解，现在可以提出几种治疗策略，这些策略可能首次专门中断其发病机制。
Graves disease represents a systemic autoimmune process targeting the thyroid, orbit, and pretibial skin. The thyroid dysfunction is treatable, but no consistently effective medical therapy has yet been described for the orbital manifestations of Graves disease, also known as thyroid-associated ophthalmopathy or thyroid eye disease. Several autoantigens are potentially relevant to the pathogenesis of thyroid eye disease. Activating antibodies generated against the thyrotropin receptor can be detected in a majority of patients, and these drive hyperthyroidism. However, stimulating antibodies against the insulin-like growth factor-1 receptor (IGF-1R) may also play a role in the extra-thyroid manifestations of GD. IGF-1R is over-expressed by orbital fibroblasts derived from patients with TED, while IGF-1R+ T and IGF-1R+ B cells are considerably more frequent in GD. Actions of several cytokines and the molecular interplay peculiar to the orbit appear to provoke the inflammation, fat expansion, and deposition of excessive extracellular matrix molecules in thyroid eye disease. Based upon these new insights, several therapeutic strategies can now be proposed that, for the first time, might specifically interrupt its pathogenesis.
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