IgG4相关性眼病（immunoglobulin G4-related ophthalmic disease, IgG4-ROD）是一种与IgG4阳性浆细胞浸润和血清IgG4水平升高相关的系统性疾病。该病的眼部表现包括泪腺、眼眶脂肪、眶下神经、眼外肌和眼睑的受累，且常伴有炎症和纤维化过程。在分子水平上，IgG4-ROD涉及多种免疫细胞和细胞因子的相互作用，包括辅助性T细胞1（T helper cell 1, Th1）、辅助性T细胞2（T helper cell 2, Th2）、调节性T细胞 (regulatory T cells, Tregs）和滤泡辅助性T细胞（follicular helper T cell, Tfh），以及由它们分泌的白细胞介素4（interleukin 4, IL-4）、白细胞介素13（interleukin 13, IL-13）和转化生长因子β（transforming growth factor-β,  TGF-β）等。这些分子通过促进B细胞活化和IgG4的产生，以及纤维化过程的发生，共同参与了IgG4-ROD的发病机制。诊断依赖于组织病理学特征，治疗通常包括糖皮质激素和免疫抑制剂，旨在控制免疫介导的炎症和纤维化，减轻症状并防止器官损伤。随着对IgG4-ROD在分子层面发病机制认识的深入，治疗策略将不断优化，进而为患者提供更为精准和有效的治疗方案，从而改善患者预后，提高患者生活质量。本文基于现有研究，总结并阐述了与IgG4-ROD致病有关的关键分子及信号通路，从分子视角对IgG4-ROD的自身免疫、纤维化及二者之间的联系与转变进行综述。

Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) is a systemic disorder characterized by the infiltration of IgG4-positive plasma cells and elevated serum IgG4 levels. The ocular symptoms of this disease can affect multiple structures, including the lacrimal gland, orbital fat, infraorbital nerves, extraocular muscles, and eyelids.These manifestations are often accompanied by inflammatory and fibrotic processes. At the molecular level, IgG4-ROD is linked to the interaction of various immune cells and cytokines. These include T helper cell 1 (Th1), T helper cell 2 (Th2), regulatory T cells (Tregs), and follicular helper T cells (Tfh), along with cytokines interleukin 4 (IL-4), interleukin 13 (IL-13), and transforming growth factor-β (TGF-β). They promote B cell activation and IgG4 production, and also facilitate the development of fibrosis. Diagnosis of IgG4-ROD is mainly based on histopathological features. Treatment typically involves the use of glucocorticoids and immunosuppressive agents, which aim to control immune-mediated inflammation and fibrosis, alleviate symptoms, and prevent organ damage. As our understanding of the molecular pathogenesis of IgG4-ROD advances, it is anticipated that treatment strategies will be continuously refined. This will enable us to offer patients more precise and effective therapeutic options, ultimately improving prognosis and quality of life. This article provides a summary and clarification of the key molecules and signaling pathways involved in the pathogenesis of IgG4-ROD. It also reviews,   from a molecular perspective, the interplay between autoimmunity and fibrosis, as well as their transformations.

目的：探讨蛋白A免疫吸附联合糖皮质激素治疗对MOG抗体相关视神经炎（MOG antibody-associated optic neuritis， MOG-ON）患者的临床疗效及安全性。方法：回顾性分析2022年6月—2024年12月在广东三九脑科医院神经内科确诊并接受蛋白A免疫吸附联合糖皮质激素治疗的7例MOG-ON患者。所有患者均接受蛋白A免疫吸附治疗（隔天1次，共5次为1个疗程）并同期联合糖皮质激素治疗。评估治疗前及治疗后3个月、6个月的视力变化、扩展伤残状态量表（expanded disability status scale，EDSS）评分变化及MOG抗体滴度变化，并记录不良反应。结果：治疗后6个月，6/7患者视力较治疗前改善，其中4/7视力改善显著。左眼LogMAR视力值从治疗前的0.20(0.14，0.70)改善至0.10(0.10，0.42)，右眼LogMAR视力值从0.30(0.19，0.47)改善至0.18(0.10，0.21)，EDSS视力评分从2.86±1.68降至1.43±1.51（P < 0.05）。治疗前血清MOG抗体滴度几何平均数为1:52.0（几何标准差GSD = 3.7），治疗后3个月降至1:8.8（GSD = 1.9）（P = 0.027），治疗后6个月降至1:13.0（GSD = 4.1）（P = 0.027）。7例患者共接受35次免疫吸附治疗，未观察到严重不良反应，仅有轻微可控的不良事件。结论：蛋白A免疫吸附联合糖皮质激素治疗能够有效降低血液中MOG抗体水平，改善MOG-ON患者的视力。

Objective: To investigate the clinical efficacy and safety of protein A immunoadsorption combined with glucocorticoid therapy in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis（MOG-ON）. Methods: A retrospective analysis was conducted on 7 patients with MOG-ON who were diagnosed and treated with protein A immunoadsorption combined with glucocorticoid therapy at the Department of Neurology，Guangdong Sanjiu Brain Hospital from June 2022 to December 2024. All patients underwent protein A immunoadsorption therapy （once every other day, with 5 sessions constituting one course） in conjunction with concurrent steroid therapy. Visual acuity changes, EDSS score changes, and MOG antibody titer changes were assessed before treatment, as well as at 3 and 6 months after treatment. Additionally, adverse events were meticulously recorded. Results: At the 6 months post-treatment mark, 6 patients （85.7%） demonstrated an improvement in visual acuity compared to their baseline levels, with 4 patients （57.1%） achieving a significant improvement. The median LogMAR visual acuity values in the left eye  improved from 0.20(0.14,0.70) to 0.10(0.10,0.42), and in the right eye, they improved from 0.30(0.19,0.47) to 0.18(0.10,0.21). MeanWhile, the EDSS visual score decreased from 2.86±1.68 to 1.43±1.51（P < 0.05）. The geometric mean serum MOG antibody titer declined from 1:52.0（GSD = 3.7） before treatment to 1:8.8（GSD = 1.9） at 3 months after treatment（P = 0.027）, and further decreased to 1:13.0（GSD = 4.1） at 6 months after treatment（P = 0.027）. A total of 35 immunoadsorption sessions were administered to the 7 patients, and no serious adverse reactions were observed; only minor and manageable adverse events occurred. Conclusion: Protein A immunoadsorption combined with glucocorticoid therapy can effectively lower serum MOG antibody levels and enhance visual outcomes in patients with MOG-ON.