CCL19, a B Cell Chemokine, Is Related to the Decrease of Blood Memory B Cells and Predicts the Clinical Response to Rituximab in Patients With Rheumatoid Arthritis
CCL19, a B Cell Chemokine, Is Related to the Decrease of Blood Memory B Cells and Predicts the Clinical Response to Rituximab in Patients With Rheumatoid Arthritis
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DOI：
10.1002/art.38023
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发表时间：
2013-08-01
影响因子：
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通讯作者：
Mariette, Xavier
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文献类型：
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作者：
Sellam, Jeremie;Rouanet, Stephanie;Mariette, Xavier
目的检测类风湿关节炎（RA）患者外周血B细胞向滑膜的迁移，以预测利妥昔单抗（RTX）的疗效。我们进行了这项研究，以调查参与B细胞运输的趋化因子的血清水平是否与B细胞耗竭前的记忆B细胞的血液水平或B细胞活化生物标志物的血清水平相关，以及趋化因子水平是否预测RTX反应性。在208例RA患者和70例对照受试者中测定了CD 27、IgD和血清B细胞活化生物标志物（类风湿因子、抗环瓜氨酸肽、游离轻链、IgG、伊加、IgM和BAFF）。采用酶联免疫吸附试验测定患者和对照组血清CCL 19、CXCL 12和CXCL 13趋化因子水平。RA患者接受RTX的第一个疗程，并在第24周根据欧洲抗风湿联盟（EULAR）标准评估反应。结果RA患者血清中各趋化因子水平均高于对照组，且与CD 27+记忆B细胞频率呈负相关。CCL 19和CXCL 13水平分别与6种血清B细胞生物标志物和4种血清B细胞生物标志物水平相关。通过单变量分析，CCL 19水平与EULAR反应正相关（OR 1.43 [95%CI 1.08-1.90]，P = 0.01）。多因素分析显示，CCL 19水平可预测RTX治疗的疗效（OR 1.48 [95%CI 1.06-2.06]，P = 0.02），但在调整自身抗体后，这一结果并不持续。结论CXCL 13和CCL 19反映了血液B细胞紊乱，其水平与其他血清B细胞生物标志物相关。因此，CXCL 13和CCL 19是RA中血清B细胞生物标志物的替代指标。血清CCL 19测定是B细胞介导的RA亚型的新标志，并可预测对RTX的临床反应。
Objective Migration of B cells from peripheral blood to the synovium in patients with rheumatoid arthritis (RA) may predict clinical response to rituximab (RTX). We undertook this study to investigate whether serum levels of chemokines involved in B cell trafficking are correlated with blood levels of memory B cells or serum levels of B cell activation biomarkers before B cell depletion and whether chemokine levels predict RTX responsiveness.Methods Blood B cell subsets were analyzed by flow cytometry (CD27, IgD), and serum B cell activation biomarkers (rheumatoid factor, anti-cyclic citrullinated peptide, free light chains, IgG, IgA, IgM, and BAFF) were measured in 208 RA patients and 70 control subjects. Serum CCL19, CXCL12, and CXCL13 chemokine levels in patients and controls were determined by enzyme-linked immunosorbent assay. The first course of RTX was administered to RA patients, and the response was evaluated at week 24 according to European League Against Rheumatism (EULAR) criteria. Results were expressed as the odds ratio (OR) and 95% confidence interval (95% CI).Results Levels of all chemokines were increased in RA patients compared with controls, and levels were inversely correlated with CD27+ memory B cell frequency. CCL19 and CXCL13 levels correlated with levels of 6 serum B cell biomarkers and 4 serum B cell biomarkers, respectively. By univariate analysis, the CCL19 level was positively associated with EULAR response (OR 1.43 [95% CI 1.08-1.90], P = 0.01). By multivariate analysis, the CCL19 level was predictive of a response to RTX (OR 1.48 [95% CI 1.06-2.06], P = 0.02), but this did not persist after adjustment for autoantibody status.Conclusion CXCL13 and CCL19 reflect blood B cell disturbances and their levels correlate with those of other serum B cell biomarkers. CXCL13 and CCL19 are, therefore, surrogate measures for serum B cell biomarkers in RA. Serum CCL19 measurement is a new hallmark of the B cell-mediated RA subtype and may predict clinical response to RTX.