Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable rare skin fragility disorder characterized by deficient dermo-epidermal adhesion due to mutations in COL7A1 gene. Modifying genes and epigenetic factors, mainly associated with inflammation, contribute to clinical severity, and are key to the design of novel effective therapies. The goal of this omics study is to expand the knowledge of the molecular mechanisms of RDEB in a homogeneous cohort with a high prevalence of hypolipidemia (low cholesterol and their transporters: HDL, LDL) correlating with inflammation. Comparative transcriptomic (RNA-seq) and lipidomic (UPLC-MS) analysis were performed on skin and serum from 8 RDEB paediatric patients enrolled in a clinical trial (NCT04153630) and 6 unaffected children. Lipidomics confirmed hypolipidemia by the decrease of 124 circulating lipids in RDEB patients, being carnitines, fatty acids, sterols and glycerophospholipids the most represented classes. Transcriptomics revealed the deregulation of 255 genes, including a significant inhibition of the leptin gene in the skin of the patients. Beyond its central role in the hypothalamus regulating feeding and energy expenditure, this protein plays an important role in the regulation of inflammation and lipid metabolism in peripheral cells. Consistently, functional enrichment analysis of leptin interactome showed significant dysregulation in key pathways related to both processes in RDEB patients (in which nutrition is compromised). This omics study provides clues to understand the role of leptin expression in skin and its mediation between inflammation and systemic lipid metabolism in RDEB. Therefore, these findings contribute to the understanding of the pathophysiology of the disease and could be relevant for developing new therapeutic approaches.

ESDR342 - The disruption of lipid metabolism and the role of leptin in the pathophysiology of Severe Recessive Dystrophic Epidermolysis Bullosa

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.