Background and Objectives CXCL13 (C-X-C motif ligand 13), also known as B-cell chemo-attractant, is an important B-cell chemokine that directly affects the migration and organization of B cells within follicles of lymphoid tissues. CXCL13 plays an important role as a major regulator of B-cell recruitment towards secondary lymphoid organs and inflammatory sites and it has recently been proposed as a serum biomarker of synovitis in patients with rheumatoid arthritis (RA). The aim of this study was to quantify CXCL13 serum levels in untreated very early polyarthritis patients to understand the dynamics of B-cell trafficking since early disease onset.
Materials and Methods CXCL13 levels were measured by ELISA in serum samples from untreated very early RA (VERA) with <6 weeks of disease duration, and compared with arthritis due to other conditions of the same duration (non-RA) (VENRA), untreated early RA (ERA) (<1 year), other early arthritis patients (non-RA) (ENRA) (<1 year), established treated RA and healthy controls (HC). Statistical analysis was performed with Mann-Whitney, Kruskal-Wallis and Spearman tests (p < 0.05).
Results We found that untreated polyarthritis patients with <6 weeks of disease duration (VERA and VENRA) had significantly higher CXCL13 serum levels in comparison with HC (p = 0.01 and p = 0.02, respectively). ERA and established RA patients also had significantly higher circulating levels of CXCL13 when compared to HC (p = 0.04 and p = 0.003, respectively), but no significant differences were observed in comparison with VERA. Moreover, no significant differences were found in ENRA patients when compared to HC. However, all patients diagnosed with RA (VERA, ERA and established RA) had significantly higher levels of CXCL13 when compared to ENRA (p < 0.05). VENRA also had significantly higher CXCL13 levels when compared to ENRA. Furthermore, no correlation was observed between CXCL13 serum levels with age, DAS28, ESR, VAS, tender and swollen joint counts.
Conclusions CXCL13 serum levels were significantly increased in untreated polyarthritis patients who subsequently resolved into a clinical diagnosis of RA. This was found in both early RA cohorts (VERA and ERA). Although VERA and VENRA (<6 weeks of disease duration) had similar CXCL13 levels, only ERA and not ENRA had significantly higher levels suggesting that chronicity was strongly associated with CXCL13 in RA patients. Overall, our results might reflect an interaction between CXCL13-producing cells (activated macrophages, follicular dendritic cells, or Th17-cells) with B-cells in secondary lymphoid tissues such as the spleen, lymph nodes and possibly in inflammatory sites i.e., joints.