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.
Rheumatology (Oxford). 2011 Mar;50(3):603-10. doi: 10.1093/rheumatology/keq337. Epub 2010 Nov 23.
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.
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.
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.
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.
ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00147966.
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。
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。
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。
RA 患者接受利妥昔单抗治疗后，血清 CXCL13 可预测 B 细胞再增殖的速度。血清 CXCL13 与单个关节测量的滑膜 CXCL13 相关，提示滑膜炎是循环 CXCL13 的重要来源。在滑膜中，CXCL13 的表达与滑膜炎标志物高度相关。
ClinicalTrials.gov，http://clinicaltrials.gov/，NCT00147966。
