Decreased levels of regulatory B cells in patients with systemic sclerosis: association with autoantibody production and disease activity

Abstract

Objective: B cell abnormalities characterized by autoantibody production and polyclonal B cell activation play an important role in the pathogenesis of SSc. IL-10 producing regulatory B (Breg) cells also play an important role in the negative immune response. We identified a human Breg cell subset that was predominantly found within the CD24(hi)CD27(+) B cell subpopulation. However, the role of Breg cells in SSc remains unknown. The aim of this study was to investigate the clinical association of Breg cells in SSc patients.

Methods: Blood IL-10 producing Breg cell levels were determined by FACS in 35 SSc patients and 30 healthy subjects. In a follow-up study, we analysed six individual dcSSc patients before and after treatment.

Results: The frequency of blood Breg cells was significantly lower in SSc patients than in healthy controls (P < 0.0001). Similarly, the frequency of CD24(hi)CD27(+) B cells was significantly lower in SSc patients than in healthy controls (P < 0.0001). SSc patients with decreased Breg cell levels often had interstitial lung disease (P < 0.05). Furthermore, Breg cell levels correlated negatively with the titre of anti-topo I antibody (Ab) and anticentromere Ab in SSc patients. For a follow-up study, Breg cell levels in dcSSc patients after treatment were found to be significantly increased compared with those before treatment (P < 0.05), accompanied by decreased disease activity. Thus, Breg cell levels were inversely correlated with disease activity of SSc.

Conclusion: These results suggest that decreased Breg cell levels may contribute to the development of SSc.

Keywords: IL-10; regulatory B cell; systemic sclerosis.