Deng YiHan, Li JianBin, Wu Rui
Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
J Inflamm Res. 2025 Apr 5;18:4741-4753. doi: 10.2147/JIR.S503144. eCollection 2025.
Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation driven by immune cell infiltration. While neutrophils have traditionally been associated with acute inflammation, emerging evidence suggests their significant role in chronic RA synovitis. Synovial pathology reports from our center reveal lymphocyte-predominant infiltration in most RA cases, with synovial neutrophils (SNs) observed in only 30% of patients. This finding suggests that neutrophil involvement in RA pathogenesis is not universal but subtype-specific, potentially linked to distinct clinical phenotypes.
We performed a retrospective analysis of synovial pathology and clinical data from 55 RA patients collected during 2023. Using both Hematoxylin-Eosin (H&E) staining and single-cell RNA sequencing, we analyzed the synovial tissue samples. Based on neutrophil counts, patients were classified into two groups: neutrophil-absent (<10 neutrophils) and neutrophil-present (≥10 neutrophils).
In this cohort of 55 RA patients, the synovial neutrophil (SN) group demonstrated significantly elevated disease activity markers, including Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP), swollen joint count (SJC28), Visual Analog Scale (VAS) pain scores, and tender joint count (TJC28) (p < 0.05 for all parameters). Synovial inflammatory infiltration and neovascularization were markedly increased in the SNs group (P < 0.05). Patients with SNs maintained higher disease activity and showed poorer therapeutic responses despite treatment with methotrexate and targeted biologics (TNF inhibitors, IL-6 inhibitors, or JAK inhibitors). Analysis revealed a positive correlation between lymphocyte and neutrophil counts, while multivariate analysis identified DAS28-CRP, synovial inflammation, and CD3+/CD68+ cell counts as predictors of SN infiltration. Single-cell RNA sequencing confirmed their significant presence in synovial tissue, supporting neutrophils' role in refractory disease.
Elevated neutrophil presence in RA synovium correlates with heightened clinical disease activity and an exacerbated inflammatory state. These findings underscore the potential significance of SNs in the pathology of RA.
类风湿性关节炎（RA）的特征是由免疫细胞浸润驱动的慢性滑膜炎。虽然传统上认为中性粒细胞与急性炎症有关，但新出现的证据表明它们在慢性RA滑膜炎中起重要作用。我们中心的滑膜病理学报告显示，大多数RA病例以淋巴细胞为主的浸润，仅30%的患者观察到滑膜中性粒细胞（SNs）。这一发现表明，中性粒细胞参与RA发病机制并非普遍现象，而是亚型特异性的，可能与不同的临床表型有关。
我们对2023年收集的55例RA患者的滑膜病理学和临床数据进行了回顾性分析。使用苏木精-伊红（H&E）染色和单细胞RNA测序，我们分析了滑膜组织样本。根据中性粒细胞计数，患者分为两组：无中性粒细胞组（<10个中性粒细胞）和有中性粒细胞组（≥10个中性粒细胞）。
在这55例RA患者队列中，滑膜中性粒细胞（SN）组的疾病活动标志物显著升高，包括基于C反应蛋白的28个关节疾病活动评分（DAS28-CRP）、肿胀关节计数（SJC28）、视觉模拟量表（VAS）疼痛评分和压痛关节计数（TJC28）（所有参数p<0.05）。SNs组的滑膜炎症浸润和新生血管形成明显增加（P<0.05）。尽管使用甲氨蝶呤和靶向生物制剂（TNF抑制剂、IL-6抑制剂或JAK抑制剂）治疗，但有SNs的患者维持较高的疾病活动度，且治疗反应较差。分析显示淋巴细胞和中性粒细胞计数之间呈正相关，而多变量分析确定DAS28-CRP、滑膜炎症和CD3+/CD68+细胞计数是SN浸润的预测因素。单细胞RNA测序证实它们在滑膜组织中大量存在，支持中性粒细胞在难治性疾病中的作用。
RA滑膜中中性粒细胞数量增加与临床疾病活动度升高和炎症状态加剧相关。这些发现强调了SNs在RA病理学中的潜在重要性。
