Department of Clinical Research Centre, The Affiliated Hospital of Guizhou Medical University, 550004, Guiyang, 550004, Guizhou Province, People's Republic of China.
Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China.
Clin Rheumatol. 2019 Jul;38(7):1831-1839. doi: 10.1007/s10067-019-04465-w. Epub 2019 Feb 26.
OBJECTIVE: This study aimed to assess the role of different subsets of circulating follicular helper T cells (Tfh), central memory (TCM), effector memory (TEM), Naïve T, chemokines, and cytokines in the pathogenesis of rheumatoid arthritis (RA). METHODS: Blood samples from RA patients (n = 44) and healthy controls (n = 37) were analyzed. The frequencies of circulating Tfh, TCM, TEM, and Naïve T cell subsets were enumerated, and the expression of co-stimulatory molecules, such as inducible co-stimulator (ICOS) and programmed death-1 (PD1), on these cells was evaluated by flow cytometry. The disease state in RA patients was assessed using the DAS28. Concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were measured. Cytokines and chemokines, such as IL-1β, TNF-α, IL-4, IL-6, IL-9, IL-17A, MCP-1, IL-10, IL-12p70, and IL-21, were measured by a cytometric beads array assay. RESULTS: The percentages of circulating PD1ICOS Tfh, PD1ICOS TEM, and PD1ICOS TCM of PBMCs from RA patients were higher than those in healthy controls. Furthermore, expression of circulating PD1ICOS Tfh, PD1ICOS TEM, and PD1ICOS TCM showed a positive correlation with DAS28. In addition, increased levels of IL-1β, IL-6, and MCP-1 were detected in the patients with RA compared to healthy controls. CONCLUSIONS: Elevated circulating T cell subsets and cytokines expression profile were observed in RA patients. IL-6, MCP-1, and IL-1β were significantly increased in RA, and PD1ICOS TEM, PD1ICOS TCM, and PD1ICOS Tfh cell subsets were positively correlated with disease activity DAS28. Therefore, PD1ICOS TEM, PD1ICOS TCM, and PD1ICOS Tfh cells might serve an important role in the progression of RA.
目的:本研究旨在评估循环滤泡辅助 T 细胞(Tfh)、中央记忆(TCM)、效应记忆(TEM)、初始 T 细胞、趋化因子和细胞因子的不同亚群在类风湿关节炎(RA)发病机制中的作用。
方法:分析 RA 患者(n=44)和健康对照者(n=37)的血样。通过流式细胞术计数循环 Tfh、TCM、TEM 和初始 T 细胞亚群的频率,并评估这些细胞上共刺激分子(如诱导共刺激分子(ICOS)和程序性死亡-1(PD1))的表达。采用 DAS28 评估 RA 患者的疾病状态。测量 C 反应蛋白(CRP)、红细胞沉降率(ESR)、抗环瓜氨酸肽(抗-CCP)和类风湿因子(RF)的浓度。通过流式细胞术微球阵列检测细胞因子和趋化因子,如 IL-1β、TNF-α、IL-4、IL-6、IL-9、IL-17A、MCP-1、IL-10、IL-12p70 和 IL-21。
结果:RA 患者外周血单个核细胞(PBMCs)中循环 PD1ICOS Tfh、PD1ICOS TEM 和 PD1ICOS TCM 的百分比高于健康对照组。此外,循环 PD1ICOS Tfh、PD1ICOS TEM 和 PD1ICOS TCM 的表达与 DAS28 呈正相关。此外,与健康对照组相比,RA 患者的 IL-1β、IL-6 和 MCP-1 水平升高。
结论:在 RA 患者中观察到循环 T 细胞亚群和细胞因子表达谱升高。IL-6、MCP-1 和 IL-1β 在 RA 中显著增加,PD1ICOS TEM、PD1ICOS TCM 和 PD1ICOS Tfh 细胞亚群与疾病活动 DAS28 呈正相关。因此,PD1ICOS TEM、PD1ICOS TCM 和 PD1ICOS Tfh 细胞可能在 RA 的进展中起重要作用。
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