AB0069 Increased expression of soluble mic-a in the synovial fluid of rheumatoid arthritis patients

Background MIC-A (Major histocompatibility complex class I chain-related gene A) 1 is a transmembrane or soluble protein that interacts with the activating NKG2D receptor. MIC-A stimulates effector responses mediated by NK and CD8 +T cells under cellular stress conditions, like cancer or infections. 2 MIC-A is also associated with autoimmune diseases (such as rheumatic disorders) characterised by immune dysregulation triggered by environmental factors, and plays important roles in immune activation and surveillance. 3 In mice, various NKG2D ligands were discovered: Rae-1, H60 and MULT1 families. 4 Objectives This study aims at investigating the potential pathological relevance of soluble MIC-A (sMIC-A) protein in inflammatory rheumatic diseases involving articular structures in humans. The expression of orthologous NKG2D ligands in mouse models of experimental joint inflammation is also quantified. Methods We collected synovial fluid (SF) from 118 subjects: 22 Rheumatoid Arthritis (RA), 13 Psoriatic Arthritis (PSOA), 12 Gout Disease (GOUT), 18 Calcium Pyrophosphate Deposition Disease (CPPD), 8 Reactive Arthritis (REA) and 45 Osteoarthritis patients. Gout and CPPD diseases were confirmed by the presence of crystals in SF. Clinical data were collected. The concentration of soluble MIC-A (sMIC-A), interleukin (IL)−1, IL-6 and IL-8 was measured by ELISA. Murine Rae-1, H60 and Mult1 transcripts were quantified by real-time quantitative PCR (RT-qPCR) in 3 models of joint inflammation: Serum Transfer Arthritis (STA), Collagen-induced arthritis (CIA) and Collagenase-Induced Osteoarthritis (CIOA). Results Significantly higher levels of sMIC-A were found in the synovial fluid of RA patients in comparison with all others diseases (p Conclusions Our data identifies synovial sMIC-A as an important player in rheumatoid arthritis compared to other rheumatic diseases and osteoarthritis. Investigations in mouse models are in agreement with this finding References [1] Bahram, Seiamak, et al. A second lineage of mammalian major histocompatibility complex class I genes. Proceedings of the National Academy of Sciences1994;91(14):6259–6263. [2] Groh, Veronika, et al. Costimulation of CD8αβ T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nature immunology2001;2(3):255. [3] Spear, Paul, et al. NKG2D ligands as therapeutic targets. Cancer Immunity Archive2013;13(2):8. [4] Carapito, Raphael, Seiamak, Bahram. Genetics, genomics, and evolutionary biology of NKG2D ligands. Immunological reviews2015;267(1):88–116. Disclosure of Interest None declared