Exploration of Serum Metabolic Signature of Erythrodermic Psoriasis Based on High-throughput Ultra-performance Liquid Chromatography Mass Spectrometry

Abstract

AbstractBackgroundErythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. The dysregulated metabolites could be tightly associated with the disease pathogenesis.ObjectivesTo explore the distinctive serum metabolic signature of EP.MethodsSerum samples of 20 EP patients and 20 matched healthy controls were collected. Non-targeted metabolomics based on a high-throughput ultra-performance liquid chromatography mass spectrometry (UHPLC-MS) was conducted. Principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA) and pathway analysis were performed.Results65 metabolites of known identity were significantly changed in EP patients compared to controls, including 24 up-regulated metabolites and 41 down-regulated metabolites. EP patients had lower levels of glycerophosphocholines, including lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and lysophosphatidyl ethanolamine (LPE). EP patients had lower levels of bile acids, including 7-ketodeoxycholic, deoxycholic and lithocholic acid. EP patients had lower esculetin and 3-hexenedioic acid levels. The area under the curve (AUC) value of esculetin, 7-ketodeoxycholic acid and 3-hexenedioic acid was higher than 0.90. Dysregulated metabolites were significantly enriched in the glycerophospholipid metabolism pathway.ConclusionsThe serum metabolic signature of EP was discovered. The down-regulated glycerophosphocholines and bile acids might take part in the development of EP. The dysregulated metabolites might be associated with damaged skin barriers and extensive skin inflammation. The metabolite differences help elucidate the development and pathogenesis of EP and they may provide insights for therapeutic interventions.