临床儿科杂志 ›› 2025, Vol. 43 ›› Issue (5): 376-382.doi: 10.12372/jcp.2025.24e1008

• 文献综述 • 上一篇    下一篇

幼年特发性关节炎相关性葡萄膜炎的发病机制与治疗

赵福林, 姜莉()   

  1. 兰州大学第一医院(甘肃兰州 730000)
  • 收稿日期:2024-09-23 录用日期:2024-11-19 出版日期:2025-05-15 发布日期:2025-05-09
  • 通讯作者: 姜莉 电子信箱:1822128433@qq.com

Pathogenesis and treatments of juvenile idiopathic arthritis-associated uveitis

ZHAO Fulin, JIANG Li()   

  1. The First Hospital of Lanzhou University, Lanzhou 730000, Gansu, China
  • Received:2024-09-23 Accepted:2024-11-19 Published:2025-05-15 Online:2025-05-09

摘要:

幼年特发性关节炎相关葡萄膜炎(JIA-U)是16岁以下儿童中一种常见的非感染性自身免疫性葡萄膜炎。其主要发病机制为遗传与环境因素的交互作用,导致机体自身免疫紊乱。在这些因素的共同作用下,JIA患者的自身免疫反应可能会破坏外周免疫耐受以及血-视网膜屏障,导致T、B细胞及其亚群浸润患者的眼组织,通过对特定的视网膜抗原产生反应、产生高度特异性的自身抗体以及分泌肿瘤坏死因子α(TNF-α)、白介素6(IL-6)等细胞因子,促进眼组织炎症的发生发展,严重时威胁患者的视力。治疗采用阶梯式策略,以皮质类固醇为一线药物,联合使用甲氨蝶呤(MTX)进行类固醇减量全身治疗,对于MTX不耐受或疗效不佳的患者,或者出现严重的视力威胁性并发症的患者,可添加或改用生物制剂类改善病情抗风湿药(bDMARDs)。TNF-α抑制剂、IL-6受体抑制剂和Janus激酶抑制剂是针对难治性JIA-U或MTX无反应的患者常用的bDMARDs,此外,T细胞共刺激调节剂和抗CD20单抗也可能对难治性JIA-U或MTX无反应的患者有效。未来研究需进一步探究这些生物制剂在JIA-U中的作用机制及安全性和有效性,以提供更有效的治疗参考。

关键词: 幼年特发性关节炎相关性葡萄膜炎, 细胞因子, 生物制剂类改善病情抗风湿药, 儿童

Abstract:

Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a prevalent non-infectious autoimmune uveitis among children under the age of 16. The principal pathogenesis lies in the interaction between genetic and environmental factors, resulting in autoimmune dysregulation within the body. Under the collective influence of these factors, the autoimmune response in JIA patients may disrupt peripheral immune tolerance and the blood-retinal barrier, leading to the infiltration of T and B cells and their subsets into the ocular tissues of patients. Through reacting to specific retinal antigens, the production of highly specific autoantibodies, and secreting cytokines such as tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), it promotes the occurrence and progression of ocular tissue inflammation, and in severe cases, poses a threat to the patient's vision. The initial treatment for JIA-U is based on a stepwise strategy, with corticosteroids as the first-line drug, combined with methotrexate (MTX) for steroid-reduced systemic therapy. For patients intolerant to MTX or with suboptimal therapeutic responses, or those presenting with severe vision-threatening complications, biological disease-modifying antirheumatic drugs (bDMARDs) can be added or substituted. TNF-α inhibitors, IL-6 receptor inhibitors, and Janus kinase inhibitors are commonly utilized bDMARDs for refractory JIA-U or patients unresponsive to MTX. Additionally, T-cell co-stimulation modulators and anti-CD20 monoclonal antibodies may also prove effective for refractory JIA-U or patients unresponsive to MTX. Future studies are requisite to further investigate the mechanism of action, safety, and efficacy of these biological agents in JIA-U, in order to provide more effective therapeutic references.

Key words: juvenile idiopathic arthritis-associated uveitis, cytokine, biologic disease modifying antirheumatic drugs, child