Plasma metabolomic profiling reflects the malnourished and chronic inflammatory state in recessive dystrophic epidermolysis bullosa. Issue 2 (August 2022)

• Record Type: Journal Article
• Authors: Chen, Ya-Fen; Lu, Hsin-Chin; Hou, Ping-Chen; Lin, Yu-Ching; Aala, Wilson Jr; Onoufriadis, Alexandros; McGrath, John A.; Chen, Ying-Lan; Hsu, Chao-Kai
• Is Part Of: Journal of dermatological science. Volume 107:Issue 2(2022)
• Page Start: 82
• Page End: 88
• Publication Date: 2022-08
• Subjects: Recessive dystrophic epidermolysis bullosa -- Plasma metabolomics -- Inflammation -- Malnutrition; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2022.07.006
• Languages: English
• ISSNs: 0923-1811

Abstract

Abstract: Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder characterized by skin fragility, chronic inflammation, malnutrition, and fibrosis. Metabolomics is an emerging investigative field that helps elucidate disease pathophysiology and identify biomarkers. However, previous metabolomic studies in RDEB are limited. Objective: To investigate the plasma metabolomic profiles in RDEB patients. Methods: We recruited 10 RDEB patients and 10 age-/gender-matched healthy controls. Peripheral blood samples were collected and plasma metabolomic profiling was performed by LC-MS/MS analysis. MS data processing and compound identification were executed by MS-DIAL . Enrichment analysis was performed by MetaboAnalyst 5.0. Results: Metabolomic analyses demonstrated that most amino acid levels were downregulated in RDEB patients, and the extent of insufficiency correlated with clinical severity. Several metabolites were dysregulated in RDEB, including glutamine and glutamate metabolism, tryptophan-to-kynurenine ratio, phenylalanine-to-tyrosine ratio, and succinate accumulation. Limitations: The study was limited by small case numbers and the unrepresentativeness of a single time-point blood sample. Conclusion: Our study demonstrated the altered metabolomic profiles in RDEB, reflecting the disease severity, the chronic inflammatory and malnourished status, while the fibrotic signatures were not evident. Highlights: RDEB is characterized by skin fragility, chronic inflammation, and fibrosis, while the metabolomic profile has not been determined. Plasma metabolomics helps elucidate disease pathophysiology and correlate nutritional status with disease severity. The metabolomic dysregulation in RDEB highlights the chronic inflammatory and malnutrition status. Several amino acids levels, including glutamine, correlate with disease severity, and highlight the potential of future glutamine supplementation in RDEB.