Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa

Nell Hirt, Enzo Manchon, Qian Chen, Clara Delaroque, Aurelien Corneau, Patrice Hemon, Safaa Saker-Delye, Pauline Bataille, Jean-David Bouaziz, Emmanuelle Bourrat, Alain Hovnanian, Helene Buanec, Fawzi Aoudjit, Hicham El Costa, Nabila Jabrane-Ferrat and Reem Al-Daccak ()
Additional contact information
Nell Hirt: Saint-Louis Hospital
Enzo Manchon: Saint-Louis Hospital
Qian Chen: Harvard Medical School
Clara Delaroque: Paris Cité University
Aurelien Corneau: Sorbonne University
Patrice Hemon: Brest University
Safaa Saker-Delye: Genethon
Pauline Bataille: Saint-Louis Hospital
Jean-David Bouaziz: Saint-Louis Hospital
Emmanuelle Bourrat: Saint-Louis Hospital
Alain Hovnanian: INSERM UMR 1163
Helene Buanec: Saint-Louis Hospital
Fawzi Aoudjit: Laval University
Hicham El Costa: Toulouse III University
Nabila Jabrane-Ferrat: Toulouse III University
Reem Al-Daccak: Saint-Louis Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood. To fill this gap, we apply systems immunology approaches using single-cell high-dimensional techniques to capture the signature of peripheral immune cells and the diversity of metabolic profiles in RDEB adults, sampled outside of any opportunistic infection and active cancer. Our study, demonstrates the particular inflammation and immunity characteristics of RDEB adults, with activated / effector T and dysfunctional natural killer cell signatures, concomitant with an overall pro-inflammatory lipid signature. Artificial intelligence prediction models and principal component analysis stress that RDEB is not solely confined to cutaneous issues but has complex systemic endotypes marked by immune dysregulation and hyperinflammation. By characterising the phenotype-endotype association in RDEB adults, our study lays the groundwork for translational interventions that could by lessening inflammation, alleviate the everlasting suffering of RDEB patients, while awaiting curative genetic therapies.

Date: 2025
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DOI: 10.1038/s41467-025-55934-7

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