title: CXCL13: a novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00147966.
authors.affiliation: 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.
authors.forename: Sanna
authors.initials: S
authors.lastname: Rosengren
authors.forename: Nathan
authors.initials: N
authors.lastname: Wei
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Kalunian
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: David L
authors.initials: DL
authors.lastname: Boyle
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D054382:Chemokine CXCL13 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D000069283:Rituximab; D013585:Synovitis / Q000097:blood* / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D000069283:Rituximab