FRI0002 S100A11 (CALGIZZARIN) IS RELEASED DURING NEUTROPHIL EXTRACELLULAR TRAPS FORMATION AND STIMULATES RELEASE OF IL-6 AND TNF IN RHEUMATOID ARTHRITIS

Background: S100A11 protein, a member of S100 family, has been associated with several autoimmune inflammatory conditions such as rheumatoid arthritis (RA). Although the pathogenesis of autoimmune diseases is not fully understood, the formation of neutrophil extracellular traps (NETs) seems to play a certain role. Recent data indicate that S100A8/A9 is released via NETosis and can further augment inflammatory responses. Objectives: The aim of our study was to examine the association of S100A11 with NETs in RA. Methods: To assess the expression of S100A11 by neutrophils of RA synovial tissue (n=8), immunofluorescence staining of S100A11 and myeloperoxidase (MPO) was performed. The levels of S100A11 and MPO in RA synovial fluid (n=23) were measured by ELISAs (RayBiotech and Abcam), and the activity of peptidyl arginine deiminases (PADs) was measured by an in-house immunoassay. NETosis was induced by adding phorbol 12-myristate 13-acetate (PMA) to neutrophils from RA patients (n=7). Release of NETs was visualised by immunocytochemistry (n=7) and the presence of S100A11 in supernatants was analysed by ELISA (RayBiotech). Neutrophils purified from healthy donors (n=5) were stimulated by S100A11 and the release of cytokines TNF and IL-6 was measured by ELISA (RayBiotech). Results: S100A11 was expressed by synovial tissue neutrophils of the RA patients (n=8). The levels of S100A11 in the synovial fluid of RA patients (n=23) correlated with the levels of a NETosis marker MPO (r=0.562, p=0.005) and with PADs activity (r=0.690, p Conclusion: Here we show for the first time that release of S100A11 by neutrophils is dependent on NETosis. Moreover, extracellular S100A11 augments the inflammatory response by inducing TNF and IL-6 secretion in neutrophils. Acknowledgments: Supported by MHCR 023728 Disclosure of Interests: Adela Navratilova: None declared, Viktor Becvar: None declared, Jiři Baloun: None declared, Dres Damgaard: None declared, Claus Henrik Nielsen: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiři Vencovský: None declared, Ladislav Senolt: None declared, Lucie Andres Cerezo: None declared, David Veigl: None declared