A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity
Issued Date
2025-02-03
Resource Type
eISSN
15409538
Scopus ID
2-s2.0-85212991529
Pubmed ID
39680367
Journal Title
The Journal of experimental medicine
Volume
222
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Journal of experimental medicine Vol.222 No.2 (2025)
Suggested Citation
Al Qureshah F., Le Pen J., de Weerd N.A., Moncada-Velez M., Materna M., Lin D.C., Milisavljevic B., Vianna F., Bizien L., Lorenzo L., Lecuit M., Pommier J.D., Keles S., Ozcelik T., Pedraza-Sanchez S., de Prost N., El Zein L., Hammoud H., Ng L.F.P., Halwani R., Saheb Sharif-Askari N., Lau Y.L., Tam A.R., Singh N., Bhattad S., Berkun Y., Chantratita W., Aguilar-López R., Shahrooei M., Abel L., Bastard P., Jouanguy E., Béziat V., Zhang P., Rice C.M., Cobat A., Zhang S.Y., Hertzog P.J., Casanova J.L., Zhang Q. A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity. The Journal of experimental medicine Vol.222 No.2 (2025). doi:10.1084/jem.20241413 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/102907
Title
A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity
Author(s)
Al Qureshah F.
Le Pen J.
de Weerd N.A.
Moncada-Velez M.
Materna M.
Lin D.C.
Milisavljevic B.
Vianna F.
Bizien L.
Lorenzo L.
Lecuit M.
Pommier J.D.
Keles S.
Ozcelik T.
Pedraza-Sanchez S.
de Prost N.
El Zein L.
Hammoud H.
Ng L.F.P.
Halwani R.
Saheb Sharif-Askari N.
Lau Y.L.
Tam A.R.
Singh N.
Bhattad S.
Berkun Y.
Chantratita W.
Aguilar-López R.
Shahrooei M.
Abel L.
Bastard P.
Jouanguy E.
Béziat V.
Zhang P.
Rice C.M.
Cobat A.
Zhang S.Y.
Hertzog P.J.
Casanova J.L.
Zhang Q.
Le Pen J.
de Weerd N.A.
Moncada-Velez M.
Materna M.
Lin D.C.
Milisavljevic B.
Vianna F.
Bizien L.
Lorenzo L.
Lecuit M.
Pommier J.D.
Keles S.
Ozcelik T.
Pedraza-Sanchez S.
de Prost N.
El Zein L.
Hammoud H.
Ng L.F.P.
Halwani R.
Saheb Sharif-Askari N.
Lau Y.L.
Tam A.R.
Singh N.
Bhattad S.
Berkun Y.
Chantratita W.
Aguilar-López R.
Shahrooei M.
Abel L.
Bastard P.
Jouanguy E.
Béziat V.
Zhang P.
Rice C.M.
Cobat A.
Zhang S.Y.
Hertzog P.J.
Casanova J.L.
Zhang Q.
Author's Affiliation
Aster CMI Hospital
A-Star, Infectious Disease Lab
l'Institut des Maladies Génétiques Imagine
Lee Kong Chian School of Medicine
Institut Mondor de Recherche Biomédicale
Necmettin Erbakan Üniversitesi
University of Sharjah
Université Libanaise
Saint George Hospital University Medical Center
King Abdulaziz City for Science and Technology
Hôpital Necker Enfants Malades
Rockefeller University
KU Leuven
AP-HP Assistance Publique - Hopitaux de Paris
Faculté de Santé
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Bilkent Üniversitesi
Hospital de Clinicas de Porto Alegre
King Saud University
Howard Hughes Medical Institute
Instituto Nacional de la Nutrición Salvador Zubiran
Universidade Federal do Rio Grande do Sul
The University of Hong Kong
Hudson Institute of Medical Research
Institut Pasteur, Paris
Hadassah University Medical Centre
Maternal and Children's Hospital ISSEMYM
Dr. Shahrooei Lab
National Institute of Population Medical Genetics (INAGEMP)
A-Star, Infectious Disease Lab
l'Institut des Maladies Génétiques Imagine
Lee Kong Chian School of Medicine
Institut Mondor de Recherche Biomédicale
Necmettin Erbakan Üniversitesi
University of Sharjah
Université Libanaise
Saint George Hospital University Medical Center
King Abdulaziz City for Science and Technology
Hôpital Necker Enfants Malades
Rockefeller University
KU Leuven
AP-HP Assistance Publique - Hopitaux de Paris
Faculté de Santé
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Bilkent Üniversitesi
Hospital de Clinicas de Porto Alegre
King Saud University
Howard Hughes Medical Institute
Instituto Nacional de la Nutrición Salvador Zubiran
Universidade Federal do Rio Grande do Sul
The University of Hong Kong
Hudson Institute of Medical Research
Institut Pasteur, Paris
Hadassah University Medical Centre
Maternal and Children's Hospital ISSEMYM
Dr. Shahrooei Lab
National Institute of Population Medical Genetics (INAGEMP)
Corresponding Author(s)
Other Contributor(s)
Abstract
Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%). Cells heterozygous for these variants display a dominant phenotype in vitro with impaired responses to IFN-α and -ω, but not -β, and viral susceptibility. Negative dominance, rather than haploinsufficiency, accounts for this dominance. Patients heterozygous for these variants are prone to viral diseases, attesting to both the dominance of these variants clinically and the importance of IFN-α and -ω for protective immunity against some viruses.