SAT0022 S100a8/a9 Is A Potent Serum and Imaging Biomarker Tool for Assessing Joint Inflammation and Destruction in Seronegative Experimental Arthritis

BackgroundSeronegative joint diseases, including psoriatic arthritis and juvenile idiopathic arthritis, are characterized by the lack of autoantibodies, which are relevant biomarkers for predicting disease activity in rheumatoid arthritis. Promising alternative biomarkers are the Damage Associated Molecular Patterns (DAMPs), S100A8, S100A9 and the heterodimer S100A8/A9. These proteins are specifically expressed and released by infiltrating phagocytes and may therefore serve as relevant biomarkers for joint inflammation and destruction in seronegative arthritis.ObjectivesIn this study we determined the biomarker potential of serum S100A8/A9 and in vivo imaging of synovial S100A8 to asses joint inflammation and damage in the IL-1 receptor antagonist deficient (IL-1Ra–/–) mice, a mouse model for seronegative arthritis in which serum autoantibodies are not correlated to disease activity.MethodsSerum levels of S100A8/A9 and various cytokines were monitored during arthritis development in IL-1Ra–/– mice using ELISA and Luminex and were correlated to macroscopic and microscopic parameters for joint inflammation and damage. Local S100A9 expression and matrix metalloproteinase (MMP) mediated cartilage damage in the ankle joints were investigated by immunohistochemistry. In addition local S100A8 and activated MMPs were monitored in vivo by optical imaging using anti-S100A8-Cy7 and AF-489-Cy7, a specific tracer for activated MMPs.ResultsStarting at week 8, serum levels of S100A8/A9 were significantly increased (1640 ± 1008 ng/ml at week 16) in IL-1Ra–/– mice compared to WT BALB/c control mice (429 ± 191 ng/ml, P =0.005) and strongly correlated to joint swelling (r =0.766, P