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Open Access Research article

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels

Jonathan D Jones1*, B JoNell Hamilton2, Gregory J Challener2, Artur J de Brum-Fernandes3, Pierre Cossette4, Patrick Liang3, Ariel Masetto3, Henri A Ménard5, Nathalie Carrier3, David L Boyle6, Sanna Rosengren7, Gilles Boire3 and William F C Rigby12

Author Affiliations

1 Division of Rheumatology, Geisel School of Medicine at Dartmouth College, One Medical Center Dr., Lebanon, NH 03756, USA

2 Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, One Medical Center Dr., Lebanon, NH 03756, USA

3 Division of Rheumatology, Sherbrooke University Hospital, 2500 University Boulevard, Sherbrooke, QC J1K 2R1, Canada

4 Department of Medicine, Sherbrooke University Hospital, 2500 University Boulevard, Sherbrooke, QC J1K 2R1, Canada

5 Research Institute of the McGill University Health Center, 2155 Guy St Montreal, QC H3H 2R9, Canada

6 Division of Rheumatology, University of California San Diego School of Medicine, 200 W Arbor Dr, La Jolla, CA 92103, USA

7 Halozyme Therapeutics, 11388 Sorrento Valley Road, San Diego, CA 92121, USA

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Arthritis Research & Therapy 2014, 16:R103  doi:10.1186/ar4552

Published: 25 April 2014

Abstract

Introduction

We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity.

Methods

Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman’s correlation analysis were utilized to determine relationships between variables.

Results

In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort.

Conclusion

Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF production.