Abstract
IntroductionWe 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.MethodsSerum 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.ResultsIn 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.ConclusionUsing 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.
Highlights
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
Log-transformed C-X-C motif chemokine 13 (CXCL13) is elevated in seropositive rheumatoid arthritis patients and correlates with immunoglobulin M rheumatoid factor The Dartmouth RA Cohort (N = 193) represents an established RA cohort with a variation in disease duration from 20 years (Table 1)
Tertile analysis of CXCL13 values confirmed that immunoglobulin M (IgM) rheumatoid factor (RF) was higher in the third than in the first and second tertiles (Figure 1C) but that immunoglobulin G (IgG) anticitrullinated peptide/protein antibody (ACPA) was not, as determined by Wilcoxon rank-sum test
Summary
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. Seropositive rheumatoid arthritis (RA) is an inflammatory disease characterized by autoantibodies (immunoglobulin G (IgG) anticitrullinated peptide/protein antibodies (ACPAs) and rheumatoid factor (RF)). These autoantibodies can appear years before the onset of clinical disease and are strongly linked to the human. A series of observations has established its production by multiple cell types in rheumatoid synovium, frequently in association with the formation of lymphoid follicular structures, including synovial T cells (but not T follicular cells) [7], monocytes/ macrophages [8] and follicular dendritic cells, endothelial cells and synovial fibroblasts [9]
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