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Background The pathogenesis of spondyloarthritis (SpA) involves activation of the innate immune system, inflammation and new bone formation. The innate immune system is activated through pattern recognition receptors including Toll like receptor 4 (TLR4). Inflammation is a result of increased production of pro-inflammatory cytokines and chemokines including tumor necrosis factor alpha (TNFα) and monocyte chemoattractant protein 1 (MCP-1). New bone formation by osteoblasts is determined by a balance between the inhibitory effect of Dickkopf-1 (DKK1) and the stimulatory effect of bone morphogenetic proteins (BMPs) including BMP2. The two cytokines IL-20 and IL-24 have been shown to link innate immune activation and tissue homeostasis.(1) Previously, we have found increased plasma levels of IL-20 and IL-24 in SpA patients. Objectives We hypothesized that IL-20 and IL-24 are secreted as part of activation of the innate immune system and affect bone homeostasis. The aim was to describe associations of IL-20 and IL-24 and disease activity and magnetic resonance imaging (MRI) scores and to identify the sources and targets of the two cytokines in SpA. Methods Patients with axial SpA (n=83) were included in the study of associations between cytokine levels and disease activity and MRI scores. Patients with peripheral SpA (n=16) were included for studying sources and targets of IL-20 and IL-24 among synovial fluid mononuclear cells (SFMCs), peripheral blood mononuclear cells (PBMCs), and fibroblast-like synoviocytes (FLSs) using lipopolysaccharide (LPS) and TNFα as positive controls. Healthy human osteoblasts were used for studying the effect of the two cytokines on mineralization using BMP2 as a positive control. The secretion of IL-20, IL-24, MCP-1 and DKK1 were measured by enzyme linked immunosorbant assays and flow cytometry, and mineralization was measured by hydroxyapatite deposition. Plasma IL-20 and IL-24 levels were analyzed with the Mann-Whitney U test and the Spearman correlation. Supernatant cytokine concentration and flow cytometry median fluorescence intensity data were calculated as ratios, log-transformed and compared with the paired or unpaired t-test. Results The plasma IL-20 and IL-24 levels were increased in SpA patients compared with healthy controls (HCs) by 57% and 83%, respectively (both p Conclusions Taken together, our findings indicate that IL-20 and IL-24 are novel links between activation of the innate immune system and new bone formation. References Rutz S et al. The IL-20 subfamily of cytokines - from host defence to tissue homeostasis. Nat Rev Immunol. 2014. Disclosure of Interest None declared

Background Lack of measures of disease activity and prognosis is a key challenge in spondyloarthritis (SpA). Several soluble biomarkers have been proposed, but very few have been found to relate to MRI activity and add to the diagnostic value of CRP.(1) Leukocytes are key players in SpA disease activity.(2) The soluble form of CD18 (sCD18) has been found to be shed from leukocytes in inflammation and to be present in the blood.(3) Objectives This study examines the association of sCD18 in the blood and SpA disease activity. Methods Plasma from a study population with 84 SpA patients at baseline and 33 patients at three-year follow-up and a control group of age and gender matched normal healthy volunteers (NHV) were studied. The samples were analyzed for sCD18 by a time resolved immunoflourometric assay (TRIFMA) using the KIM185 antibody as capture antibody and the KIM127 antibody as detection antibody as previously described.(3) Results The level of sCD18 was decreased in plasma from SpA patients compared to plasma from NHV (p Conclusions sCD18 is associated with clinical findings, CRP and SIJ MRI activity in SpA. sCD18 could be a novel disease activity marker in SpA directly measuring leukocyte activity. References Maksymowych WP. Biomarkers in spondyloarthritis. Current rheumatology reports. 2010;12(5):318-24. Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011;377(9783):2127-37. Gjelstrup LC, Boesen T, Kragstrup TW, Jorgensen A, Klein NJ, Thiel S, et al. Shedding of large functionally active CD11/CD18 Integrin complexes from leukocyte membranes during synovial inflammation distinguishes three types of arthritis through differential epitope exposure. J Immunol. 2010;185(7):4154-68. Disclosure of Interest None Declared