Plasma Metabolomics Of Vogt-koyanagi-harada Disease Identifies Potential Diagnostic Biomarkers

Background and purposeUveitis is a common autoimmune disease.Vogt-koyanagis-harada(VKH)syndrome is one of the common types of uveitis in China.The diagnostic criteria for uveitis are still controversial.Metabolomics investigates the substrates of various metabolic pathways and their molecular compounds that can reflect changes under pathological conditions.The main purpose of this study was to compare the differences of plasma metabolites VKH patients with healthy controls to investigate potential diagnostic plasma biomarkers for VKH disease.MethodsUltra-High-Performance Liquid Tandem Chromatography Quadrupole Time of Flight Mass Spectrometry(UHPLC-QTOF/MS)was performed on plasma samples.Multivariate statistical Analysis including Principal Component Analysis(PCA)and Orthogonal partial least squares Discriminant Analysis(OPLS-DA)were used to screen differential metabolic biomarkers.Hierarchical cluster analysis was used to analysisthe disturbed metabolic pathways.The area under the curve(AUC)was adopted to identify the potential diagnostic biomarkers.ResultsThe metabolic phenotype of VKH patients showed a significant difference compared to healthy controls.Fifteen differentially expressed metabolites were identified between active VKH patients and healthy controls and nine DEMs were found between inactive VKH patients and healthy controls after controlling variable importance in the projection(VIP)value>1 and false discovery rate(FDR)<0.05.D-mannose,stearic acid and L-lysine were shown to be potential diagnostic biomarkers which can discriminate active VKH patients from healthy controls with a diagnostic performance with AUC=0.965,0.936 and 0.910 respectively in independent diagnosis and an AUC=0.999 when combined.Sarcosine was recognized as an independent potential biomarker which could distinguish inactive VKH patients from healthy controls.ConclusionsThis study reveals a significant difference of plasma metabolic phenotype and identifies diagnostic biomarkers for VKH disease.Changes in the metabolic profile may provide clues towards the pathophysiology of VKH disease.