Plasma metabolomic profiling reflects the malnourished and chronic inflammatory state in recessive dystrophic epidermolysis bullosa

TY - JOUR

T1 - Plasma metabolomic profiling reflects the malnourished and chronic inflammatory state in recessive dystrophic epidermolysis bullosa

AU - Chen, Ya Fen

AU - Lu, Hsin Chin

AU - Hou, Ping Chen

AU - Lin, Yu Ching

AU - Aala, Wilson

AU - Onoufriadis, Alexandros

AU - McGrath, John A.

AU - Chen, Ying Lan

AU - Hsu, Chao Kai

N1 - Funding Information: This study was financially supported partly by National Cheng Kung University Hospital, Taiwan (20210068 and 20220063) and partly by Higher Education Sprout Project, Ministry of Education to the Headquarters of University Advancement at National Cheng Kung University, Taiwan. Dr. Ying-Lan Chen is also supported by Taiwan MOST Young Scholar Fellowship Einstein Program (109–2636-B-006–009 and 110–2636-B-006–008). The mass spectrometry analysis was supported by the Academia Sinica Metabolomics Core Facility at the Agricultural Biotechnology Research Center of Academia Sinica, supported by Academia Sinica Core Facility and Innovative Instrument Project (AS-CFII-108–108). We thank Dr. Shu-Ming Tsao of ez-Omics Co., Ltd for data processing and bioinformatics analysis. Funding Information: This work was financially supported by National Cheng Kung University Hospital , Taiwan ( 20210068 and 20220063 ) and partly by Higher Education Sprout Project, Ministry of Education to the Headquarters of University Advancement at National Cheng Kung University, Taiwan. Publisher Copyright: © 2022 Japanese Society for Investigative Dermatology

PY - 2022/8

Y1 - 2022/8

N2 - 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.

AB - 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.

KW - Inflammation

KW - Malnutrition

KW - Plasma metabolomics

KW - Recessive dystrophic epidermolysis bullosa

UR - http://www.scopus.com/inward/record.url?scp=85135138898&partnerID=8YFLogxK

U2 - 10.1016/j.jdermsci.2022.07.006

DO - 10.1016/j.jdermsci.2022.07.006

M3 - Article

AN - SCOPUS:85135138898

SN - 0923-1811

VL - 107

SP - 82

EP - 88

JO - Journal of Dermatological Science

JF - Journal of Dermatological Science

IS - 2

ER -