Department of Rheumatology, Aarhus University Hospital , Aarhus , Denmark.
Scand J Rheumatol. 2014;43(2):91-100. doi: 10.3109/03009742.2013.803149. Epub 2013 Aug 28.
The aim of this study was to measure, in early rheumatoid arthritis (RA) patients, the concentration of CC-chemokine ligand 19 (CCL19) in plasma and the cell-surface expression of CC-chemokine receptor 7 (CCR7) on circulating monocytes and CD4+ T lymphocytes and to analyse correlations with disease activity and 5-year radiographic progression.
In disease-modifying anti-rheumatic drug (DMARD)-naïve RA patients (disease duration < 6 months), we measured plasma CCL19 by enzyme-linked immunosorbent assay (ELISA) (n = 160) and CCR7 cell-surface expression on monocytes and CD4+ T lymphocytes by flow cytometry (n = 40) at baseline and after 1 year of treatment with methotrexate (MTX) or methotrexate+cyclosporin A (MTX/CyA). Radiographic progression was scored by the van der Heijde-modified Total Sharp Score (TSS) from 0 to 5 years.
Increased baseline CCL19 (median 85 pg/mL, range 31-1008 pg/mL, p = 0.01) decreased after 1 year (median 31 pg/mL, range 31-1030 pg/mL, p < 0.001) and 5 years (median 31 pg/mL, range 31-247 pg/mL, p < 0.001) to a level below the controls (n = 45) (median 60 pg/mL, range 31-152 pg/mL). Baseline plasma CCL19 levels [p = 0.011, 95% confidence interval (CI) 0.0030-0.0176], anti-cyclic citrullinated peptide (anti-CCP) antibody status (p = 0.002, 95% CI 0.61-2.38), and TSS > 0 at baseline (p < 0.001, 95% CI 1.21-3.16) were independent predictors of 5-year radiographic progression evaluated by multiple logistic regression in contrast to never smoked, C-reactive protein (CRP), gender, age, number of tender (NTJ) and swollen joints (NSJ), and 28-joint Disease Activity Score (DAS28). Increased CCR7 expression on monocytes (p = 0.008) correlated to CRP (p = 0.006, r = 0.52) and normalized (n = 15) after 1 year (p = 0.02).
In DMARD-naïve RA patients, CCL19 plasma level and CCR7 surface expression on monocytes were upregulated and normalized after 1 year of treatment. Increased baseline plasma CCL19 level, anti-CCP antibody status, and TSS > 0 at baseline correlated independently with 5-year radiographic progression.
本研究旨在测量早期类风湿关节炎（RA）患者血浆中趋化因子配体 19（CCL19）的浓度以及循环单核细胞和 CD4+T 淋巴细胞表面表达的趋化因子受体 7（CCR7），并分析其与疾病活动度和 5 年放射学进展的相关性。
在接受疾病修饰抗风湿药物（DMARD）治疗的 RA 患者（病程<6 个月）中，我们通过酶联免疫吸附试验（ELISA）（n=160）测量基线和接受甲氨蝶呤（MTX）或 MTX+环孢素 A（MTX/CyA）治疗 1 年后的血浆 CCL19（n=40）。通过 van der Heijde 改良总 Sharp 评分（TSS）从 0 到 5 年对放射学进展进行评分。
基线 CCL19 升高（中位数 85pg/mL，范围 31-1008pg/mL，p=0.01），治疗 1 年后（中位数 31pg/mL，范围 31-1030pg/mL，p<0.001）和 5 年后（中位数 31pg/mL，范围 31-247pg/mL，p<0.001）下降至低于对照组（n=45）（中位数 60pg/mL，范围 31-152pg/mL）。基线血浆 CCL19 水平（p=0.011，95%置信区间（CI）0.0030-0.0176）、抗环瓜氨酸肽（抗-CCP）抗体状态（p=0.002，95%CI 0.61-2.38）和基线 TSS>0（p<0.001，95%CI 1.21-3.16）是通过多变量逻辑回归分析预测 5 年放射学进展的独立预测因素，而从不吸烟、C 反应蛋白（CRP）、性别、年龄、压痛关节数（NTJ）和肿胀关节数（NSJ）以及 28 关节疾病活动度评分（DAS28）则不是。单核细胞上 CCR7 表达增加（p=0.008）与 CRP（p=0.006，r=0.52）相关，且在治疗 1 年后正常化（n=15）（p=0.02）。
在接受 DMARD 治疗的 RA 患者中，CCL19 血浆水平和单核细胞上的 CCR7 表面表达在治疗 1 年后上调并正常化。基线时较高的血浆 CCL19 水平、抗-CCP 抗体状态和 TSS>0 与 5 年放射学进展独立相关。
