Fiche publication
Date publication
novembre 2025
Journal
Journal of human immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak
,
Dr CARAPITO Raphaël
Tous les auteurs :
van der Linden TJ, Arts RJW, Biggs CM, Habibi L, Batlle-Masó L, van Laarhoven A, Scheepmaker LM, Yousefi P, Gómez-Raccio AC, Alizadeh Z, Mulders-Manders CM, Oever JT, Schuurs-Hoeijmakers J, Alipour-Olyei N, Molitor A, Di Giovanni D, Carapito R, Bahram S, Seminario G, Bezrodnik L, Momenilandi M, Shahrooei M, Bustamante J, Aksentijevich I, Kastner D, Fazlollahi MR, Colobran R, Turvey SE, van de Veerdonk FL, Casanova JL, Boisson B, Bardoel BW, Spaan AN
Lien Pubmed
Résumé
Human OTULIN haploinsufficiency predisposes to life-threatening necrosis of the skin and lungs. Disease is triggered by infectious agents, typically , as well as unknown etiologies. We describe and characterize six unrelated patients who carry rare, predicted deleterious variants of in heterozygosity. In addition to staphylococcal infections, the disease in the patients is elicited by previously underappreciated triggers, including mechanical or iatrogenic traumas and pseudomonal or clostridial infections. Severe necrosis of the lungs and/or skin are clinical hallmarks of their disease. By combining allele characterizations and functional studies in patients' cells, we demonstrate that the patients suffer from OTULIN haploinsufficiency. We provide guidance for assessing heterozygous variants in diagnostic settings by evaluating measures of predicted deleteriousness. The clinical course of the patients expands the genotypic and phenotypic spectrum of OTULIN haploinsufficiency and provides, in the light of a broadening of triggers, leads for therapeutic interventions.
Mots clés
OTULIN, Staphylococcus aureus, haploinsufficiency, linear ubiquitin, necrosis
Référence
J Hum Immun. 2025 11 3;1(4):
