Rheumatoid Arthritis Related B-Cell Changes Are Found Already in the Risk-RA Phase

Abstract

Anti-cyclic citrullinated peptide2 (CCP2) antibody positivity in rheumatoid arthritis (RA) and in the predisease phase, together with the success of B-cell depletion, support a crucial role for B cells in RA pathogenesis. Yet, knowledge of B cells in the transition from autoimmunity to RA is limited, and therefore we here investigated B-cell changes during the risk-RA phase. B-cell phenotypes in 18 CCP2-positive risk-RA individuals with musculoskeletal complaints were studied, parallel with ten CCP2-positive RA patients and nine healthy controls. Nine of the risk-RA individuals progressed to RA. B-cell phenotypes were investigated using spectral flow cytometry. The results demonstrate that unswitched and switched memory B-cell frequencies in the risk-RA cohort were more similar to controls than RA patients. Yet, risk-RA progressors displayed an early activation profile amongst naïve B cells. Deeper characterization of the memory compartment revealed expansion of CD27-negative IgG+ B cells both in RA compared with controls (p = 0.0172) and in risk-RA progressors versus non-progressors (p = 0.0295). Overall, we demonstrate that the phenotypic distribution of B cells is altered in the risk-RA phase. This includes changes in CD27-negative class-switched B cells, which have been attributed to autoreactive and anergic features implicating a possible contribution to RA development.