FRI0011 IL-10-Producing Regulatory B Cells are Decreased in Systemic Sclerosis

• Published in: Annals of the rheumatic diseases Vol. 74; no. Suppl 2; p. 423
• Main Authors: Mavropoulos, A., Simopoulou, T., Varna, A., Liaskos, C., Katsiari, C., Bogdanos, D., Sakkas, L.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2015
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2015-eular.3117

BackgroundSystemic 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 autoimmunityObjectivesTo investigate the significance of IL-10-producing Bregs in SScMethodsThe 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 analysisResultsMemory 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.ConclusionsThis 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 InterestNone declared