4.5 Article

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

期刊

JOURNAL OF DERMATOLOGY
卷 49, 期 10, 页码 1012-1019

出版社

WILEY
DOI: 10.1111/1346-8138.16495

关键词

effector B cells; IL-6; IL-10; regulatory B cells; systemic sclerosis

资金

  1. Ministry of Education, Science, and Culture of Japan [19K08768]
  2. Grants-in-Aid for Scientific Research [19K08768] Funding Source: KAKEN

向作者/读者索取更多资源

This study investigated the levels of effector and regulatory B cells in patients with SSc and found that an increase in effector B cells and a decrease in regulatory B cells were associated with the severity of SSc. These results suggest that B cells play an important role in the pathogenesis of SSc.
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.

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