Knee joint-fluid proteomics reveals potential diagnostic and prognostic biomarkers to distinguish between septic vs. autoimmune arthritis in children 2505

Description The evaluation of children with suspected septic arthritis is challenging due to the high rate of negative cultures and the consideration of inflammatory and reactive conditions. We assessed the potential clinical value of knee joint-fluid proteomics in guiding clinical decision-making in twelve children diagnosed with presumed septic arthritis. Joint-fluid cytokines and antibodies levels were measured to identify novel immune biomarkers to enhance the diagnostic confidence for children with culture negative diagnosis for any infectious agent. Metagenomics sequencing revealed presence of Streptococcus pyogenes and Staphylococcus aureus species in 50% (6/12) cases, whereas the remaining 50% were negative for any pathogen. Neutrophils count and CRP level were similar in infection negative and positive group. The inflammatory cytokines including IL-4, IL-17A, MCP-1, IL-8, IL-2, IL-1b, IL-6, TNF-a, etc. were significantly elevated in the joint-fluid of children with bacteremia whereas, children without bacteremia exhibited strong signature of IgG autoantibodies i.e. Collagens III, II, Nup62, Factor I, dsDNA, histones, Jo-1, scl-70, Ro/SS-A, SmDs, in their joint-fluid. Distinct cytokine (p = 0.009) and autoantibody (p = 0.04) profiles of two groups provided crucial information on potential autoimmune conditions. Thus, proteomic analysis rapidly guided the diagnosis of children with inflammatory arthritis, Juvenile idiopathic arthritis (JIA) and Post-Streptococcal Reactive Arthritis. Funding Sources The Hartwell Foundation Topic Categories Translational and Interventional Immunology (TI)