A targeted proteomics screen reveals serum and synovial fluid proteomic signature in patients with gout

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Objective: To characterize the inflammatory proteome in both serum and synovial fluid (SF) of patients with gout, in comparison to healthy controls and individuals with osteoarthritis (OA), by utilizing a high-quality, high-throughput proteomic analysis technique. Methods: Using the Olink Target 48 Inflammation panel, we measured serum concentrations of 45 inflammatory proteins in gout, OA, and healthy controls. We analyzed protein levels in SF samples from gout and OA, performed ROC curve analyses to identify diagnostic biomarkers, evaluate efficacy, and set cut-off values. Additionally, A protein-protein interaction (PPI) network was used to study protein relationships and significance. Results: We have delineated the proteomic landscape of gout and identified 20 highly differentially expressed proteins (DEPs) in the serum of gout patients in comparison to that of healthy controls, which included VEGF-A, MMP-1, TGF-α, and OSM with corresponding area under the curve (AUC) values of 0.95, 0.95, 0.92, and 0.91 respectively. For the analysis of synovial fluid, 6 proteins were found to be elevated in gout in contrast to osteoarthritis (OA), among which IP-10, VEGF-A, IL-8, and MIP-3β had corresponding AUC values of 0.78, 0.78, 0.76, and 0.75 respectively. The protein-protein interaction (PPI) network analysis identified significantly prominent pathways in gout. Conclusion: This research marks a significant advancement in elucidating the inflammatory profile present in the serum and synovial fluid of individuals suffering from gout. Our discoveries have identified several novel proteins in both serum and synovial fluid that are potential biomarkers for diagnostic purposes and are believed to have critical roles as pathogenic factors in the pathophysiology of gout.

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