A Comparative Metabolomic Evaluation of Behcet's Disease with Arthritis and Seronegative Arthritis Using Synovial Fluid.
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.
Department of Internal Medicine, Division of Rheumatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Joong Kyong
JK
Ahn
Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
Sooah
S
Kim
Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
Jungyeon
J
Kim
Department of Internal Medicine, Division of Rheumatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Jiwon
J
Hwang
Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
Kyoung Heon
KH
Kim
Department of Medicine, Division of Rheumatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Hoon-Suk
HS
Cha
D000293:Adolescent; D000328:Adult; D000368:Aged; D001168:Arthritis / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D001528:Behcet Syndrome / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D018384:Oxidative Stress; D013582:Synovial Fluid / Q000378:metabolism*; D055815:Young Adult
D015415:Biomarkers