Abstract
Behcet’s disease (BD) with arthritis is often confused with seronegative arthritis (SNA) because of shared clinical symptoms and the lack of definitive biomarkers for BD. To investigate possible metabolic patterns and potential biomarkers of BD with arthritis, metabolomic profiling of synovial fluid (SF) from 6 patients with BD with arthritis and 18 patients with SNA was performed using gas chromatography/time-of-flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. A total of 123 metabolites were identified from samples. Orthogonal partial least square-discriminant analysis showed clear discrimination between BD with arthritis and SNA. A set of 11 metabolites were identified as potential biomarkers for BD using variable importance for projection values and the Wilcoxon-Mann-Whitney test. Compared with SNA, BD with arthritis 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 BD with arthritis (sensitivity, 100%; specificity, 61.1%). This is the first report to present potential biomarkers from SF for discriminating BD with arthritis from SNA. The metabolomics of SF may be helpful in searching for potential biomarkers and elucidating the clinicopathogenesis of BD with arthritis.
Highlights
Behcet’s disease (BD) is a chronic, complex systemic vasculitis of unknown etiology characterized by orogenital ulcers, uveitis, and arthritis, which is more prevalent in Korea, China, Japan, and Turkey [1]
To determine whether it was possible to distinguish between metabolic profiles of BD with arthritis and seronegative arthritis (SNA) using processed data from the GC/TOF MS, principal component analysis (PCA) and Orthogonal partial least square-discriminative analysis (OPLS-DA) were carried out in this study
The metabolite profiles of BD with arthritis and SNA were distinctly separated on the score plot of OPLS-DA (Fig 1A)
Summary
Behcet’s disease (BD) is a chronic, complex systemic vasculitis of unknown etiology characterized by orogenital ulcers, uveitis, and arthritis, which is more prevalent in Korea, China, Japan, and Turkey [1]. Immunologic abnormalities, and PLOS ONE | DOI:10.1371/journal.pone.0135856. Metabolomic Profiling of Behcet's Disease with Arthritis the Korean Government. Experiments were performed using facilities of the Institute of Biomedical Science and Food Safety at the Korea University Food Safety Hall. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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