Thyroid Eye Disease Center at the Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan 48105, USA.
Curr Opin Ophthalmol. 2011 Sep;22(5):385-90. doi: 10.1097/ICU.0b013e3283499446.
Thyroid eye disease (TED) is a poorly understood autoimmune manifestation most commonly associated with Graves' disease. Current nonspecific treatment paradigms offer symptomatic improvement but fail to target the underlying pathogenic mechanisms, and thus do not significantly alter the long-term disease outcome. The purpose of this review is to provide an update of the current understanding of the immunopathogenesis of TED and explore these mechanisms for targeted immunotherapy.
Orbital fibroblasts are integral to the pathogenesis of TED and may modulate immune responses by production of cytokines and hyaluronan in response to activation of shared autoantigens including thyrotropin receptor and insulin-like growth factor-1 receptor. Bone marrow-derived fibrocytes share many of these phenotypic and functional features, suggesting a link between systemic and site-specific disease. Use of targeted immunotherapies in TED is limited, though data from the use Rituximab (RTX), a B-cell depleting agent, are encouraging. Sustained clinical response has been seen with RTX in several reports, despite return of peripheral B-cell levels to pretreatment levels. Additionally, this response appears to be independent of cytokine and antibody production, suggesting modulation of antigen presentation as a mechanism of its effect.
Progressive advances in the understanding of the immunopathogenesis of TED continue to spur clinical trials utilizing targeted immune therapies. Continued understanding of the molecular mechanisms of disease will expand potential treatments for TED patients and obviate the need for reconstructive surgical therapies.
甲状腺眼病（TED）是一种自身免疫性疾病，与格雷夫斯病（Graves' disease）最为常见。目前，非特异性治疗方案仅能改善症状，但无法针对潜在的致病机制，因此无法显著改变疾病的长期预后。本综述旨在阐述 TED 的免疫发病机制的最新研究进展，并探讨针对这些机制的靶向免疫治疗。
眼眶成纤维细胞是 TED 发病机制的重要组成部分，通过对包括促甲状腺激素受体和胰岛素样生长因子-1 受体在内的共同自身抗原的激活，产生细胞因子和透明质酸，从而调节免疫反应。骨髓来源的纤维细胞具有许多相似的表型和功能特征，提示系统性疾病与局部疾病之间存在联系。尽管使用抗 B 细胞耗竭剂利妥昔单抗（RTX）的数据令人鼓舞，但 TED 中靶向免疫疗法的应用有限。几项研究报告表明，RTX 治疗可获得持续的临床缓解，尽管外周 B 细胞水平恢复至治疗前水平。此外，这种反应似乎与细胞因子和抗体产生无关，提示抗原呈递的调节可能是其作用机制之一。
对 TED 免疫发病机制的理解不断深入，推动了靶向免疫疗法的临床试验。对疾病分子机制的深入理解将扩大 TED 患者的潜在治疗方法，并避免重建性手术治疗的需要。
