Characteristics of regulatory B10 cells in patients with rheumatoid arthritis with different disease status

Abstract

In the present study, the frequency and function of B10 cells in patients with rheumatoid arthritis (RA) was examined. A total of 24 healthy controls and 97 patients with RA were enrolled in the present study. Among the 75 patients with an active disease status, 51 patients received either no treatment or were treated with non-steroidal anti-infammatory drugs (NSAIDs) only, while 24 patients underwent a disease relapse. Flow cytometry was used to assess the frequency of CD19+ CD24hi CD38hi interleukin (IL)-10+ cells stimulated by lipopolysaccharide plus CD40L for 48 h, followed by re-stimulation with phorbol myristate acetate and ionomycin for 5 h. The correlation of CD19+ CD24hi CD38hi IL-10+-cell frequency with clinical/laboratory characteristics and with levels of infammatory cytokines were assessed along with the effects of CD19+ CD24hi CD38hi cells on the proliferation and tumor necrosis factor α expression of CD3+ T cells. The median frequency of IL-10-competent cells among the CD19+ B cells was significantly increased among patients with RA with active disease. However, a sub-group of patients with a high disease status that received no treatment/NSAIDs exhibited a signif-cantly lower frequency (≤1% IL-10+ B cells). These patients exhibited longer symptom duration, a greater number of tender and swollen joints and a higher patient global visual analogue scale and disease activity score in 28 joints-C reactive protein. Functional assays further demonstrated that B10 cells from the sub-group with ≤1% IL-10+ B cells secreted significantly lower levels of IL-10 and exerted a significantly decreased suppressive effect on CD3+ T-cell proliferation and tumor necrosis factor-α production. The frequency and functional heterogeneity of B10 cells in patients with RA at different disease stage suggested that further investigation on the underlying mechanism of the generation and function of B10 cells in patients with RA is required prior to use in clinical practice.