FRI0012 IL-10-Producing Regulatory B Cell Deficiency is a Feature of Psoriatic Arthritis. (9th June 2015) - Mavropoulos, A.
Abstract : Background: In mice, IL-10-producing regulatory B cells (Bregs) suppress inflammatory immune responses and adoptive transfer of Bregs reduced imiquimod-induced psoriatic skin lesions in CD19(-/-) mice (1). Inflammatory Tcells and cytokines (Th1, Th17, TNFa) play a significant role in the pathogenesis of psoriasis and psoriatic arthritis (PsA). Objectives: To assess the phenotypic and functional characteristics of Breg subsets, CD19(pos)CD27(pos)CD24(high) memory and CD19(pos)CD24(high)CD38(high) transitional Bregs in patients with PsA. Methods: Peripheral blood mononuclear cells were isolated from 25 patients with PsA and 15 normal controls (NCs). The expression of surface CD19, CD24, CD27 and CD38 and cytoplasmic IL-10 by Bregs was examined by flow cytometry following bacterial CpG (ODN2006) stimulation using fluorochrome-conjugated monoclonal antibodies. Results: Memory and transitional B regs were significantly decreased in PsA patients compared to NCs, respectively (2.2±0.42 vs 6.1±0.5, p =0.01 and 0.8±0.31 vs 1.5±0.21, p =0.03, respectively). The ratio of CD24(high) to CD24(low) B cells was also significantly decreased in PsA patients compared to NCs (p<0.001). IL-10 expressing Bregs after Toll-like receptor (TLR)-9 stimulation were primarily detected within memory than transitional B cell subsets in NCs; both subsets were significantly decreased in PsA compared to NCs (p<0.05). After ODN2006 stimulation for 24hrs, CD24(low) B cells from NCs are capable to produce IL10, in sharp contrast to CD24(low) from PsA which are unable to express IL10 (p=0.037). Conclusions: This is the first study to demonstrate that Bregs are reduced and functionally impaired after innate stimulus in PsA. This suggests that Bregs may be implicated in the development of PsA. References: Yanaba K et al. J leuk Biol 2013;94:563 Disclosure of Interest: None declared