Division of Rheumatology, Ospedale Pediatrico Bambino Gesù IRCCS, Roma, Italy.
Ph.D. Course "Immunology, Molecular Medicine and Applied Biotechnology", University of Rome Tor Vergata, Rome, Italy.
Front Immunol. 2023 Sep 19;14:1254139. doi: 10.3389/fimmu.2023.1254139. eCollection 2023.
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that may cause joint destruction and disability. The pharmacological treatment of RA aims at obtaining disease remission by effectively ceasing joint inflammation and arresting progressive bone erosions. Some patients present bone lesions accrual even after controlling joint inflammation with current therapies. Our study aimed to analyze lymphocyte subsets and levels of circulating cytokines in patients with RA with progressive bone erosions.
We enrolled 20 patients with a diagnosis of RA and 12 healthy donors (HD). Patients with RA were divided into patients with bone erosions (RA-BE+) and without bone erosions (RA-BE-). Lymphocyte subsets in peripheral blood were evaluated by flow cytometry. Circulating cytokines levels were evaluated by protein array.
The distribution of lymphocyte subsets was not able to separate HD from AR patients and RA-BE+ and RA-BE- in cluster analysis. We observed a significant expansion of CXCR5 PD1 T peripheral helper cells (Tph cells) and a reduction in both total memory B cells and switched memory B cells in RA patients compared to HD. We observed an expansion in the frequency of total B cells in RA-BE+ patients compared to RA-BE- patients. Unsupervised hierarchical clustering analysis of 39 cytokines resulted in a fairly good separation of HD from RA patients but not of RA-BE+ patients from RA-BE- patients. RA-BE+ patients showed significantly higher levels of IL-11 and IL-17A than RA-BE- patients.
We show that patients with progressive erosive disease are characterized by abnormalities in B cells and in cytokines with a proven role in bone reabsorption. Understanding the role played by B cells and the cytokine IL-11 and IL-17A in progressive erosive disease can help identify novel biomarkers of erosive disease and design treatment approaches aimed at halting joint damage in RA.
类风湿关节炎（RA）是一种炎症性自身免疫性疾病，可能导致关节破坏和残疾。RA 的药物治疗旨在通过有效停止关节炎症和阻止进行性骨侵蚀来实现疾病缓解。即使在使用当前疗法控制关节炎症后，仍有一些患者出现骨损伤累积。我们的研究旨在分析进展性骨侵蚀的 RA 患者的淋巴细胞亚群和循环细胞因子水平。
我们纳入了 20 名 RA 患者和 12 名健康供体（HD）。将 RA 患者分为有骨侵蚀（RA-BE+）和无骨侵蚀（RA-BE-）的患者。通过流式细胞术评估外周血淋巴细胞亚群。通过蛋白质阵列评估循环细胞因子水平。
聚类分析无法通过淋巴细胞亚群分布将 HD 与 AR 患者和 RA-BE+和 RA-BE-区分开来。与 HD 相比，我们观察到 RA 患者外周辅助性 T 细胞（Tph 细胞）的 CXCR5 PD1 表达显著增加，总记忆 B 细胞和转换记忆 B 细胞减少。与 RA-BE-患者相比，RA-BE+患者总 B 细胞频率增加。对 39 种细胞因子进行无监督层次聚类分析，结果相当好地将 HD 与 RA 患者区分开来，但不能将 RA-BE+患者与 RA-BE-患者区分开来。RA-BE+患者的 IL-11 和 IL-17A 水平明显高于 RA-BE-患者。
我们表明，进展性侵蚀性疾病患者的 B 细胞和在骨吸收中起作用的细胞因子存在异常。了解 B 细胞和细胞因子 IL-11 和 IL-17A 在进展性侵蚀性疾病中的作用，可以帮助确定侵蚀性疾病的新生物标志物，并设计旨在阻止 RA 关节损伤的治疗方法。
