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.