Changes in peripheral CD19(+)Foxp3(+) and CD19(+)TGFβ(+) regulatory B cell populations in rheumatoid arthritis patients with interstitial lung disease.

Abstract

Although the role of regulatory B cells (Bregs) in rheumatic disease has gained increasing attention, two lesser-known Breg subsets that express either Foxp3 or transforming growth factor beta (TGFβ) are rarely examined in studies of rheumatic disease. This study investigates the association between the relative proportions of CD19(+)Foxp3(+) and CD19(+)TGFβ(+) Bregs, and clinical indicators of disease severity in rheumatoid arthritis (RA) patients with or without interstitial lung disease (ILD). A total of 31 RA patients (14 with and 17 without ILD) and 26 healthy control subjects were included. All subjects did not have other autoimmune disease except RA, tumor, active infection, or a history of related drug administration. Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed by flow cytometry (FCM). The relationship between the relative proportions of CD19(+)Foxp3(+) and CD19(+)TGFβ(+) Bregs and their associations to RA and ILD incidence, as well as disease severity assessed by common clinical indicators, were then examined. Our analyses revealed RA patients had significantly lower proportions of peripheral CD19(+)Foxp3(+) and CD19(+)TGFβ(+) Bregs as compared to healthy controls. While no association was observed between CD19(+)Foxp3(+) Bregs and ILD incidence, patients with ILD had a substantially lower percentage of CD19(+)TGFβ(+) Bregs compared to RA patients without ILD. In addition, CD19(+)Foxp3(+) Bregs were negatively correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in RA patients, whereas CD19(+)TGFβ(+) Bregs were only correlated with CRP in RA patients with ILD. Furthermore, there was a negative association between CD19(+)Foxp3(+) Bregs and disease severity scores, which was not found in analyses with CD19(+)TGFβ(+) Bregs. The proportions CD19(+)Foxp3(+) and CD19(+)TGFβ(+) Bregs were significantly decreased in RA patients, particularly in those with ILD complications, suggesting that Breg phenotypes may have different functions in the pathogenesis of RA and ILD.