A Comparative Metabolomic Evaluation Of Behcet'S Disease With Arthritis And Seronegative Arthritis Using Synovial Fluid

Background Behcet9s disease (BD) is a chronic, complex systemic vasculitis of unknown etiology characterized by orogenital ulcers, uveitis, and arthritis. Arthritis and arthralgias in BD are known to be the most common rheumatologic findings with a prevalence ranging from 40 to 70%. However, arthritis in BD is often confused with seronegative arthritis (SNA) including seronegative spondyloarthropathy (SNSpA) and seronegative rheumatoid arthritis (SNRA) because of shared clinical symptoms and the lack of definitive biomarkers for BD. Objectives The purpose of this study was to evaluate the metabolomic profiling of synovial fluid (SF) from patients with arthritis in BD and SNA to investigate possible metabolic patterns and potential biomarkers for arthritis in BD. Methods SF samples were collected from BD patients with arthritis ( n =6, mean age 34.8±16.4 years), SNSpA ( n =13, mean age 30.9±11.0 years), and SNRA ( n =5, mean age 65.8±10.7 years). Metabolomic profiling was performed by gas chromatography/time-of-flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. Results A total of 123 metabolites were identified from samples. Orthogonal partial least square-discriminant analysis showed clear discrimination between arthritis in BD and SNA. A set of 11 metabolites were identified as potential biomarkers for arthritis in BD using variable importance for projection values and the Wilcoxon-Mann-Whitney test. Compared with SNA, arthritis in BD exhibited relatively high levels of glutamate, valine, citramalate, leucine, methionine sulfoxide, glycerate, phosphate, lysine, isoleucine, urea, and citrulline. There were two markers identified, elevated methionine sulfoxide and citrulline, that were associated with increased oxidative stress, providing a potential link to BD-associated neutrophil hyperactivity. Glutamate, citramalate, and valine were selected and validated as putative biomarkers for arthritis in BD (sensitivity, 100%; specificity, 61.1%). Conclusions This is the first report to present potential biomarkers from SF for discriminating arthritis in BD from SNA. The metabolomics of SF may be helpful in searching for potential biomarkers and elucidating the clinicopathogenesis of arthritis in BD. Acknowledgements This work was supported by the Advanced Biomass Ru0026D Center of Korea (2011-0031353), the National Research Foundation of Korea funded by the Ministry of Education (NRF-2013R1A1A2059103), and a grant of the Korea Health Technology Ru0026D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health u0026 Welfare (HI14C2285), which are funded by the Korean Government. Experiments were performed using facilities of the Institute of Biomedical Science and Food Safety at the Korea University Food Safety Hall. Disclosure of Interest None declared