Rao Peishi, Jin Shanzhao, Zhang Baozhen, Li Ru, Sun Xiaolin, Zhang Liang, Li Zhanguo
Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis, Beijing, China.
General Practice Department, Beijing Jishuitan Hospital, Beijing, China.
Clin Rheumatol. 2025 Jul 30. doi: 10.1007/s10067-025-07565-y.
Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by persistent synovitis. The synovial inflammation observed in RA exhibits significant heterogeneity among patients.
To examine the relationship between major immune cell infiltration profiles in synovium and both local synovitis and systemic manifestations of RA.
This cross-sectional study enrolled 22 RA patients (mean disease duration: 7.1 years). Synovial biopsies were assessed using the Krenn synovitis scoring system (no/low/high-grade) and immunohistochemical pathotyping (lympho-myeloid, diffuse-myeloid, pauci-immune). Clinical parameters, including the Disease Activity Score-28 (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and autoantibody status, were systematically analyzed.
Immunohistochemical analysis identified three distinct synovial pathotypes, characterized by specific distributions of CD3⁺ T cells, CD68⁺ macrophages, CD20⁺ B cells, and CD138⁺ plasma cells. Synovitis severity, classified using the Krenn scoring system, demonstrated significant differences in synovial inflammation and stromal hyperplasia. High-grade synovitis exhibited significantly increased infiltration of CD20⁺ B cells (p = 0.025) and CD138⁺ plasma cells (p = 0.034) compared to non-inflamed tissues. Pathotype distribution analysis revealed a predominance of the pauci-immune subtype in the no-synovitis group (59.1%), whereas the lympho-myeloid subtype became progressively more prevalent with increasing synovitis severity (31.8% overall).ESR, CRP, and DAS28, were significantly correlated with synovial immune cell infiltration and synovitis severity, whereas no significant association was observed between synovitis and RA associated autoantibodies such as anti-cyclic citrullinated peptide (anti-CCP) or rheumatoid factor (RF).
These findings underscore the complex interactions between synovial infiltrating immune cells, synovitis severity, and systemic disease activity, providing valuable insights for the development of personalized RA management strategies. Key Points •This study characterizes synovial immune infiltrates in relation to synovitis severity and systemic disease activity in RA •High-grade synovitis, as assessed by the Krenn scoring system, is associated with increased infiltration of immune cells, such as CD20⁺ B cells and CD138⁺ plasma cells, contributing to more severe inflammation and joint destruction. •The distribution of synovial pathotypes (lympho-myeloid, diffuse-myeloid, pauci-immune) correlates with synovitis severity, providing insights into potential molecular subtypes that could influence clinical phenotypes and treatment responses in RA.
类风湿关节炎（RA）是一种以持续性滑膜炎为特征的全身性自身免疫性疾病。RA患者中观察到的滑膜炎症在患者之间表现出显著的异质性。
研究滑膜中主要免疫细胞浸润谱与RA局部滑膜炎和全身表现之间的关系。
这项横断面研究纳入了22例RA患者（平均病程：7.1年）。使用Krenn滑膜炎评分系统（无/低/高度）和免疫组织化学病理分型（淋巴细胞-髓细胞型、弥漫性髓细胞型、少免疫型）对滑膜活检进行评估。系统分析了包括疾病活动评分28（DAS28）、红细胞沉降率（ESR）、C反应蛋白（CRP）和自身抗体状态在内的临床参数。
免疫组织化学分析确定了三种不同的滑膜病理类型，其特征在于CD3⁺T细胞、CD68⁺巨噬细胞、CD20⁺B细胞和CD138⁺浆细胞的特定分布。使用Krenn评分系统分类的滑膜炎严重程度在滑膜炎症和基质增生方面表现出显著差异。与非炎症组织相比，高度滑膜炎表现出CD20⁺B细胞（p = 0.025）和CD138⁺浆细胞（p = 0.034）浸润显著增加。病理类型分布分析显示，无滑膜炎组中少免疫亚型占优势（59.1%），而淋巴细胞-髓细胞亚型随着滑膜炎严重程度的增加逐渐更为普遍（总体为31.8%）。ESR、CRP和DAS28与滑膜免疫细胞浸润和滑膜炎严重程度显著相关，而滑膜炎与RA相关自身抗体如抗环瓜氨酸肽（抗CCP）或类风湿因子（RF）之间未观察到显著关联。
这些发现强调了滑膜浸润免疫细胞、滑膜炎严重程度和全身疾病活动之间的复杂相互作用，为制定个性化的RA管理策略提供了有价值的见解。要点•本研究描述了与RA滑膜炎严重程度和全身疾病活动相关的滑膜免疫浸润情况•通过Krenn评分系统评估的高度滑膜炎与免疫细胞浸润增加有关，如CD20⁺B细胞和CD138⁺浆细胞，导致更严重的炎症和关节破坏。•滑膜病理类型（淋巴细胞-髓细胞型、弥漫性髓细胞型、少免疫型）的分布与滑膜炎严重程度相关，为可能影响RA临床表型和治疗反应的潜在分子亚型提供了见解。
