Abstract
BackgroundAlterations 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.Results122 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 naïve 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 naïve 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.ConclusionsThe onset of RA is characterized by higher percentages and absolute numbers of naïve B cells and lower numbers of plasmablasts and double negative memory B cells compared to established RA. Naïve B cells could represent a promising biomarker of outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-014-0028-1) contains supplementary material, which is available to authorized users.
Highlights
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
In the last years, B cells have been shown to play a key role in the pathogenesis of rheumatoid arthritis (RA), as suggested by rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity as marker of disease severity that may precede the onset of symptoms by many years [1,2,3,4]; B cell depletion therapy has proven to be effective in seropositive patients [5]
We have demonstrated that B cells from the synovial compartment of RA patients express higher levels of Zeta-chain-associated protein kinase 70 (ZAP-70) compared to B cells from patients with osteoarthritis and positively correlate with the synovial levels of autoantibodies, IL-6 and B-cell activating factor (BAFF) [14]
Summary
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. B cells have been shown to play a key role in the pathogenesis of rheumatoid arthritis (RA), as suggested by rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity as marker of disease severity that may precede the onset of symptoms by many years [1,2,3,4]; B cell depletion therapy has proven to be effective in seropositive patients [5]. There is a great need for biomarkers that can help the physicians to understand the pathogenetic mechanisms underlying this “therapeutic window” Among these biomarkers, B cell subsets may be key drivers involved in the early phases of the disease
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