CXCL13：利妥昔单抗治疗后 B 细胞恢复和类风湿关节炎患者滑膜炎的新型生物标志物。

CXCL13: a novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis.

机构信息

Division of Rheumatology, Department of Medicine, Allergy and Immunology, University of California at San Diego School of Medicine, 9500 Gilman Drive, Mail Code 0656, La Jolla, CA 92093-0656, USA.

出版信息

Rheumatology (Oxford). 2011 Mar;50(3):603-10. doi: 10.1093/rheumatology/keq337. Epub 2010 Nov 23.

DOI:10.1093/rheumatology/keq337

PMID:21098574

Abstract

OBJECTIVES

The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. Its behaviour in the context of B-cell depletion therapy and reconstitution was studied during treatment of RA with rituximab.

METHODS

Serum samples from 20 RA patients were analysed for CXCL13, RF-IgM and anti-CCP by ELISA before and 2 and 6 months following rituximab treatment. B cells were monitored by flow cytometry. Gene expression in blood and synovial biopsies was determined by qPCR.

RESULTS

Patients with detectable B cells at 6 months had significantly higher levels of CXCL13 and RF-IgM and slightly higher levels of anti-CCP throughout the study, including at baseline, compared with patients with undetectable B cells at 6 months. Conversely, 10 of 12 patients with high baseline CXCL13 had detectable circulating B cells at 6 months, whereas no B cells could be detected at 6 months in patients with low baseline CXCL13. Synovial CXCL13 expression at baseline correlated significantly with serum CXCL13 levels, and the synovium of patients with high serum CXCL13 expressed elevated levels of IL-1β, IL-8, MMP1 and MMP3. In addition, synovial CXCL13 expression correlated significantly with several synovial inflammatory markers.

CONCLUSIONS

Serum CXCL13 is predictive of the rate of B-cell repopulation following a course of rituximab in RA. Serum CXCL13 correlates with synovial CXCL13 measured at a single joint, suggesting synovitis as an important source of circulating CXCL13. Within the synovium, CXCL13 expression is highly correlated with markers of synovitis.

TRIAL REGISTRATION

ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00147966.

摘要

目的

B 细胞趋化因子 CXCL13 是类风湿关节炎（RA）滑膜炎的一种潜在血清生物标志物。本研究旨在探讨利妥昔单抗治疗 RA 期间，B 细胞耗竭治疗及重建过程中 CXCL13 的行为表现。

方法

采用 ELISA 法检测 20 例 RA 患者利妥昔单抗治疗前、治疗后 2 个月及 6 个月的血清 CXCL13、RF-IgM 和抗-CCP 水平，采用流式细胞术监测 B 细胞，采用 qPCR 检测血液和滑膜活检组织中的基因表达。

结果

6 个月时可检测到 B 细胞的患者，与 6 个月时不可检测到 B 细胞的患者相比，其 CXCL13、RF-IgM 水平显著更高，抗-CCP 水平在整个研究过程中（包括基线时）也略高。相反，12 例基线 CXCL13 较高的患者中，有 10 例在 6 个月时可检测到循环 B 细胞，而基线 CXCL13 较低的患者在 6 个月时则无法检测到 B 细胞。基线时滑膜 CXCL13 的表达与血清 CXCL13 水平显著相关，且血清 CXCL13 水平较高的患者的滑膜表达较高水平的 IL-1β、IL-8、MMP1 和 MMP3。此外，滑膜 CXCL13 的表达与多个滑膜炎症标志物显著相关。