Pandya Jayesh M, Lundell Anna-Carin, Andersson Kerstin, Nordström Inger, Theander Elke, Rudin Anna
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden.
Department of Rheumatology, Skåne University Hospital Lund and Malmö, Lund University, Lund, Sweden.
Arthritis Res Ther. 2017 Feb 2;19(1):20. doi: 10.1186/s13075-017-1224-1.
We have recently analyzed the profile of T-cell subtypes based on chemokine receptor expression in blood from untreated early rheumatoid arthritis (ueRA) patients compared to healthy controls (HC). Here, we compared the levels of the respective chemokines in blood plasma of ueRA patients with those of HC. We also studied the association of chemokine levels with the proportions of circulating T-cell subsets and the clinical disease activity.
Peripheral blood was obtained from 43 patients with ueRA satisfying the ACR 2010 criteria and who had not received any disease-modifying anti-rheumatic drugs (DMARD) or prednisolone, and from 14 sex- and age-matched HC. Proportions of T helper cells in blood, including Th0, Th1, Th2, Th17, Th1Th17, TFh, and regulatory T cells, were defined by flow cytometry. Fifteen chemokines, including several CXCL and CCL chemokines related to the T-cell subtypes as well as to other major immune cells, were measured in blood plasma using flow cytometry bead-based immunoassay or ELISA. Clinical disease activity in patients was evaluated by assessing the following parameters: Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), swollen joint counts (SJC), tender joint counts (TJC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The data were analyzed using multivariate factor analyses followed by univariate analyses.
Multivariate discriminant analysis showed that patients with ueRA were separated from HC based on the blood plasma chemokine profile. The best discriminators were CXCL9, CXCL10, CXCL13, CCL4, and CCL22, which were significantly higher in ueRA compared to HC in univariate analyses. Among the chemokines analyzed, only CXCL10 correlated with multiple disease activity measures, including DAS28-CRP, DAS28-ESR, CDAI, SJC in 66 joints, CRP, and ESR.
High circulating levels of CXCL10 in the plasma of ueRA patients and the association with the clinical disease activity suggests that CXCL10 may serve as a disease activity marker in early rheumatoid arthritis.
我们最近分析了未治疗的早期类风湿关节炎（ueRA）患者与健康对照（HC）血液中基于趋化因子受体表达的T细胞亚群概况。在此，我们比较了ueRA患者与HC血浆中相应趋化因子的水平。我们还研究了趋化因子水平与循环T细胞亚群比例及临床疾病活动度之间的关联。
从43例符合美国风湿病学会（ACR）2010标准且未接受过任何改善病情抗风湿药物（DMARD）或泼尼松龙治疗的ueRA患者以及14例年龄和性别匹配的HC中获取外周血。通过流式细胞术确定血液中T辅助细胞的比例，包括Th0、Th1、Th2、Th17、Th1Th17、滤泡辅助性T细胞（TFh）和调节性T细胞。使用基于流式细胞术微珠的免疫测定法或酶联免疫吸附测定法（ELISA）检测血浆中15种趋化因子，包括几种与T细胞亚群以及其他主要免疫细胞相关的CXCL和CCL趋化因子。通过评估以下参数来评价患者的临床疾病活动度：28个关节疾病活动评分（DAS28）、临床疾病活动指数（CDAI）、肿胀关节计数（SJC）、压痛关节计数（TJC）、C反应蛋白（CRP）和红细胞沉降率（ESR）。数据采用多因素分析，随后进行单因素分析。
多变量判别分析显示，基于血浆趋化因子谱可将ueRA患者与HC区分开来。最佳判别因子为CXCL9、CXCL10、CXCL13、CCL4和CCL22，在单因素分析中，ueRA患者的这些因子水平显著高于HC。在所分析的趋化因子中，只有CXCL10与多种疾病活动度指标相关，包括DAS28-CRP、DAS28-ESR、CDAI、66个关节的SJC、CRP和ESR。
ueRA患者血浆中CXCL水平升高且与临床疾病活动度相关，这表明CXCL10可能作为早期类风湿关节炎的疾病活动度标志物。
