Fiche publication
Date publication
novembre 2026
Journal
Journal of human immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak
,
Dr CARAPITO Christine
,
Dr CARAPITO Raphaël
Tous les auteurs :
Idani A, Bibi-Triki S, Stemmelen T, Radosavljevic M, Grenot P, Hirschler A, Bernard A, Rosenzwajg M, Yang J, Eischen A, Naegely L, Macquin C, Pichot A, Spinnhirny P, Hanauer A, Alipour-Olayei N, Cherrier T, Kolmer A, Paul N, Olson RJ, Morava E, Miao Z, Carapito C, Rostami P, Parvaneh N, Shahrooei M, Molitor A, Carapito R, Bahram S
Lien Pubmed
Résumé
Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis.
Référence
J Hum Immun. 2026 11 2;2(6):e20250234
