Transitional and CD21− PD-1+ B cells are associated with remission in early rheumatoid arthritis

Abstract

Background: Early initiation of effective treatment is associated with positive long-term prognosis for patients with rheumatoid arthritis (RA). Currently, there are no biomarkers in clinical use to predict treatment response. A predictor of treatment response may be the B-cell compartment, as this is altered in RA patients, making it a potential candidate for predicting treatment response. In this study, we sought to identify B-cell subset(s) at diagnosis that might be associated with Clinical Disease Activity Index (CDAI) remission at 24-week follow-up. Methods: Seventy early RA patients from the NORD-STAR trial, recruited from two Swedish sites, and 28 matched healthy controls, were included in this spin-off study. In NORD-STAR, all patients were randomized to methotrexate (MTX) combined with 1) prednisolone, 2) anti-TNF (certolizumab-pegol), 3) CTLA4-Ig (abatacept), or 4) anti-IL-6R (tocilizumab). Circulating B-cell subsets at diagnosis were assessed by flow cytometry. The primary outcome measure was remission according to CDAI ≤ 2.8. A multivariate two-part discriminant analysis was performed to assess whether B-cell subpopulations at diagnosis could predict remission at 24 weeks. Subsequent univariable statistical analyses were performed using t-tests, Mann-Whitney U, or Kruskal-Wallis tests, as appropriate. Correlations were analyzed using Spearman or Pearson tests, depending on data type. The impact of specific B-cell populations on remission at week 24 was assessed using logistic regression models. The logistic regression model was also used to simultaneously visualize the sensitivity and specificity of the model for all possible values of the exposure (B-cell subpopulations) in predicting the outcome. Results: Patients who achieved CDAI remission at 24 weeks had higher proportions of transitional (p < 0.01) and CD21− PD-1+ (p < 0.01) B cells at diagnosis compared to those who did not. When the two B-cell populations were combined, the sensitivity and specificity for remission, including all treatment arms, were 59% and 86%, respectively. Stratification of the patients by treatment arm revealed a significant negative correlation between the proportion of transitional B cells at baseline and disease activity after 24 weeks of treatment with either MTX and prednisolone or anti-IL-6R. Conclusions: Our results indicate that transitional and CD21− PD-1+ B cells are associated with remission in early RA. Clinical trial number: Not applicable.