Cytokine‐producing B‐cell balance associates with skin fibrosis in patients with systemic sclerosis

Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. Over 90% of patients with SSc are positive for autoantibodies. In addition, the serum levels of B-cell activating factor, a potent B-cell stimulator, are correlated with SSc severity and activity. Thus, B cells play an important role in SSc pathogenesis. However, two opposing B-cell subsets exist: effector B cells (Beff) and regulatory B cells (Breg). Interleukin (IL)-6-producing Beff have been shown to promote scleroderma in a mouse model, whereas IL-10-producing Breg inhibit scleroderma development. In the present study, we investigated the clinical association of effector and regulatory B cells in patients with SSc. The blood levels of IL-6-producing Beff and IL-10-producing Breg were measured in 30 patients with SSc and 21 healthy subjects by flow cytometry. The frequency of IL-6-producing Beff in the blood was significantly (p < 0.0001) elevated in patients with SSc (median, 56.2%; range, 35.3-81.3%) compared with that in healthy controls (median, 41.3%; range, 21.0-61.3%). In contrast, the frequency of IL-10-producing Breg in the blood was significantly (p < 0.05) decreased in patients with SSc (median, 1.4%; range, 0.5-2.8%) compared with that in healthy controls (median, 2.0%; range, 1.1-3.8%). The Beff/Breg ratio was significantly increased in patients with SSc. In addition, the Beff/Breg ratio was positively correlated with the skin score and extent of interstitial lung disease. These results suggest that dysregulation of effector and regulatory B-cell balance contributes to SSc pathogenesis.