Memory B cell subsets and plasmablasts are lower in early than in long-standing Rheumatoid Arthritis

Background: Alterations of B cell subset distribution have been described in the peripheral blood (PB) of rheumatoid arthritis (RA) patients, but no data are available on differences between the onset and the established phases of the disease. The purpose of the study was to clarify whether a peculiar distribution of B cell subsets characterizes RA onset, thus leading to a more favorable clinical response to treatment, and to evaluate the possible association of a particular B cell subpopulation with response to therapy. Results: 122 RA patients were enrolled: 25 had symptom duration less than 3 months and were defined as having "very early RA" (VERA), and 43 had symptom duration from more than 3 months up to one year (early-RA: ERA). The other 54 RA patients had long-standing RA (LSRA). At baseline and at 6-month follow-up visit peripheral blood samples were collected and analyzed by flow cytometry for the distribution of circulating B cell subsets by staining with surface markers CD45, CD19, CD38, CD27 and IgD and intracellular marker ZAP70. VERA and ERA patients showed higher percentages and absolute counts of circulating antigen inexperienced naive B cells (IgD + CD27-) and lower percentages and absolute numbers of double negative (IgD-CD27-) memory B cells and plasmablasts (CD38 + CD27+) compared to LSRA patients. At the multivariate analysis, a higher frequency of naive B cells (IgD + CD27-) at baseline arose as significant predictor of CDAI remission, together with "having VERA disease" and a low disease activity at baseline. Conclusions: The onset of RA is characterized by higher percentages and absolute numbers of naive B cells and lower numbers of plasmablasts and double negative memory B cells compared to established RA. Naive B cells could represent a promising biomarker of outcome.