Abstract
The diagnosis of Vogt-Koyanagi-Harada (VKH) disease is mainly based on a complex clinical manifestation while it lacks objective laboratory biomarkers. To explore the potential molecular biomarkers for diagnosis and disease activity in VKH, we performed an untargeted urine metabolomics analysis by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Through univariate and multivariate statistical analysis, we found 9 differential metabolites when comparing VKH patients with healthy controls, and 26 differential metabolites were identified when comparing active VKH patients with inactive VKH patients. Pathway enrichment analysis showed that glycine, serine and threonine metabolism, and arginine and proline metabolism were significantly altered in VKH versus healthy controls. Lysine degradation and biotin metabolism pathways were significantly altered in active VKH versus inactive VKH. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the combination of acetylglycine and gamma-glutamylalanine could differentiate VKH from healthy controls with an area under the curve (AUC) of 0.808. A combination of ureidopropionic acid and 5′-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR) had an excellent AUC of 0.958 for distinguishing active VKH from inactive VKH. In summary, this study identified abnormal metabolites in urine of patients with VKH disease. Further studies are needed to confirm whether these metabolites are specific for this disease.
Highlights
Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder affecting the eye, hair, skin, auditory, and central nervous system (Yang et al, 2007; Sakata et al, 2014)
To identify potential diagnostic biomarkers, receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic potential of differential metabolites and the area under the curve (AUC) was calculated (Zou et al, 2007)
To further investigate specific diagnostic biomarkers, a two-step method was performed: (1) differential metabolites were subjected to a stepwise binary logistic regression analysis to establish a combined model; (2) ROC curve analysis was carried out to measure the diagnostic performance of the combined metabolites
Summary
Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder affecting the eye, hair, skin, auditory, and central nervous system (Yang et al, 2007; Sakata et al, 2014). Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease currently based on clinical manifestations while it lacks laboratory biomarkers (Read et al, 2001; Yang P. et al, 2018). It is accessible and bears no need of invasive sampling. The molecular activity in urine doesn’t change much after sampling which shows a better stability, and it is a relatively clean medium which contains few interfering proteins (Schmidt, 2009; Li et al, 2014; Dinges et al, 2019). Little is known about urine metabolite composition in clinical uveitis and this was the purpose of the study presented here
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