Background and objectives Newly identified B-cell related markers beyond autoantibodies may help better stratifying and predicting the heterogeneous outcome of rheumatoid arthritis (RA). The aim of this study was to investigate whether serum levels of the B-cell chemoattractant CXCL13 can implement information provided by traditional laboratory markers in patient with early RA.

Materials and methods The pathological correlates of CXCL13, acute phase reactants and autoantibodies were determined in 60 RA patients with paired serum and synovial tissue samples. Baseline associations, responsiveness to change and predictive validity for response to therapy were assessed in a prospective cohort of 213 early RA patients undergoing treatment with methotrexate aiming at low disease activity (LDA).

Results In paired serum and synovial samples, CXCL13 covaried with tissue levels of the chemokine (rho 0.56, p = 0.01) and was the only laboratory marker able to discriminate high degrees of B-cell infiltration (AUROC [95% CI] 0.74 [0.61 to 0.85]). Serum CXCL13 showed lower correlation with disease activity and lower responsiveness to change after 2 months of therapy compared with acute phase reactants. Levels were increased in anti-citrullinated protein antibody-positive (ACPA) subjects, approximatively half of whom had high CXCL13 (3^rd tertile, >106 pg/ml), and correlated with rheumatoid factor (RF) titres. High CXCL13 alone independently predicted failure to achieve LDA after 12 months of therapy with an adjusted OR (95% CI) of 2.87 (1.42 to 5.82) (p = 0.003), a high negative predictive value (NPV) (79.9%, 95% CI 72.1% to 86.3%) but a quite low positive predictive value (PPV) (50.7%, 95% CI 38.4% to 63%). Combining high CXCL13 with autoantibody positivity (ACPA and/or RF) significantly increased the PPV (61%, 95% CI 44.5% to 75.8%) without affecting the NPV (77.2%, 95% CI 69.9% to 83.4%).

Conclusions In early RA patients treated with conventional synthetic disease-modifying anti-rheumatic drugs, serum CXCL13 appears a novel lymphoid-linked biomarker holding non-redundant information with respect to acute phase reactants and autoantibodies, and able to stratify patients into different prognostic subgroups.