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FRI0011 IL-10-Producing Regulatory B Cells are Decreased in Systemic Sclerosis
  1. A. Mavropoulos,
  2. T. Simopoulou,
  3. A. Varna,
  4. C. Liaskos,
  5. C. Katsiari1,1,
  6. D. Bogdanos,
  7. L. Sakkas
  1. Rheumatology, Medical School, University of Thessaly, Larissa, Greece

Abstract

Background Systemic sclerosis (SSc) is a characterized by extensive fibrosis and a plethora of autoantibodies, the latter being indicative of breakage of tolerance. Regulatory B cells (Bregs) producing interleukin (IL)-10 play a significant role in suppressing inflammatory immune responses and preventing autoimmunity

Objectives To investigate the significance of IL-10-producing Bregs in SSc

Methods The study groups consisted of 45 patients with SSc (12 with early SSc, 33 with established SSc [of whom 16 with SSc-associated lung fibrosis,SSc-LF]) and 10 healthy controls (HCs). As a disease controls for SSc-LF, 12 patients with rheumatoid arthritis-associated LF (RA-LF) were included. Peripheral blood monunuclear cells were isolated from patients and controls. Phenotypic analysis of immature/transitional Bregs (CD19+CD24highCD38high) and memory Bregs (Cd19+CD27+Cd24high) was carried out by flow cytometry using FACS Calibur. The function of bregs was evaluated by IL-10 expression after Bcell culture with toll-like receptor (TLR)9 stimulation, and flow cytometry analysis

Results Memory Bregs were decreased in early SSc (1.85±0.38), established SSc (1.6±0.88), and SSc-LF (1.52±0.17) compared to HCs (6.3±0.49, p<0.001). There were more decreased in diffuse cutaneous SSc (dcSSc) than limited cutaneous SSc (lcSSc), but not significantly so. The lowest percentage of memory Bregs was in dcSSc-LF (1.36±0.16). Memory Bregs were also numerically decreased in RA-LF compared to HCs (1.58±0.26, p<0.001). Transitional Bregs were also numerically decreased in early SSc, and established SSc compared to HCs (p<0.02). Bregs IL-10 expression after Toll-like receptor (TLR)-9 stimulation (innate stimulus) was impaired in SSc, particularly in SSc-LF.

Conclusions This is the first study to demonstrate that Bregs are reduced and functionally impaired in SSc, particularly SSc-LF. The impaired IL-10 production after innate stimulus may have clinical implications. The impairment of Bregs along with the reported increased expression of the stimulatory Bcell receptor CD19 in SSc support B cell autoaggression in SSc. These findings may offer a new therapeutic strategy for SSc, namely expanding Bregs ex-vivo and re-administering them to patients with SSc.

Disclosure of Interest None declared

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