title: Metabolic Disturbances in Adult-Onset Still's Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis.
abstract: OBJECTIVE
  Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still's disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome.
  
  
  METHODS
  Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites.
  
  
  RESULTS
  Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05).
  
  
  CONCLUSIONS
  Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis.
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.|Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Institute of Molecular Biology, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Han-Ju
authors.initials: HJ
authors.lastname: Chien
authors.affiliation: Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Hsieh
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.|Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hung
authors.affiliation: Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.|Institute of Molecular Biology, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Chien-Chen
authors.identifier: http://orcid.org/0000-0002-7133-8266
authors.initials: CC
authors.lastname: Lai
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D011446:Prospective Studies; D016706:Still's Disease, Adult-Onset / Q000378:metabolism* / Q000473:pathology*