| Title: |
A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity |
| Authors: |
Al Qureshah, Fahd; Le Pen, Jérémie; de Weerd, Nicole; Moncada-Velez, Marcela; Materna, Marie; Lin, Daniel; Milisavljevic, Baptiste; Vianna, Fernanda; Bizien, Lucy; Lorenzo, Lazaro; Lecuit, Marc; Pommier, Jean-David; Keles, Sevgi; Ozcelik, Tayfun; Pedraza-Sanchez, Sigifredo; de Prost, Nicolas; El Zein, Loubna; Hammoud, Hassan; Ng, Lisa F.P.; Halwani, Rabih; Saheb Sharif-Askari, Narjes; Lau, Yu Lung; Tam, Anthony; Singh, Neha; Bhattad, Sagar; Berkun, Yackov; Chantratita, Wasun; Aguilar-López, Raúl; Shahrooei, Mohammad; Abel, Laurent; Aiuti, Alessandro; Al-Muhsen, Saleh; Alcántara-Garduño, Ana Bertha; Andreakos, Evangelos; Arias, Andrés; Feldman, Hagit Baris; Bastard, Paul; Bolze, Alexandre; Borghesi, Alessandro; Bousfiha, Ahmed; Brodin, Petter; Christodoulou, John; Cobat, Aurélie; Colobran, Roger; Condino-Neto, Antonio; Duvlis, Sotiriјa; Duval, Xavier; Dündar, Munis; Fakhreddine, Soha; Fellay, Jacques; Flores, Carlos; Franco, José Luis; Gorochov, Guy; Gregersen, Peter; Hagin, David; Herrera, María Teresa; Hung, Ivan Fan-Ngai; Jouanguy, Emmanuelle; Lau, Yu-Lung; Leung, Daniel; Le-Voyer, Tom; Mansouri, Davood; Mercado-García, Jesús; Meyts, Isabelle; Mogensen, Trine; Novelli, Antonio; Novelli, Giuseppe; Okada, Satoshi; Ozcelik, Firat; de Diego, Rebeca Perez; Perez-Tur, Jordi; Pesole, Graziano; Puel, Anne; Renia, Laurent; Resnick, Igor; Rodríguez-Gallego, Carlos; Sbeity, Manal; Sedighzadeh, Sahar; Soler-Palacín, Pere; Spaan, András; Tangye, Stuart; Tayoun, Ahmad Abou; Temel, Şehime Gülsün; Thorball, Christian; Torktaz, Ibrahim; Trouillet-Assant, Sophie; Turvey, Stuart; Uddin, Furkan; Vianna, Fernanda Sales Luiz; Vinh, Donald; Zabaleta-Martínez, Oscar; Zhang, Qian; Zhang, Shen-Ying; Casanova, Jean-Laurent; Eng, Chanreaksmey; Bun, Kimrong; Oum, Mengheng; Piola, Patrice; Tarantola, Arnaud; Channa, Mey; Duong, Veasna; Buchy, Philippe; Gorman, Chris; Crabol, Yoann; Dussart, Philippe; Bunleat, M.; Panha, M.; Sim, M.Kanarith; Bunnakea, Em; Laurent, Denis; Sothy, Heng; Santy, Ky; Douangnouvong, Anousone; Chommanam, Danoy; Phakhounthong, Khansoudaphone; Vongsouvath, Manivanh; Seephone, Malee; Sibounheunang, Bountoy; Rattanavong, Sayaphet; Davong, Viengmon; Vongsouvath, Malavanh; Mayxay, Mayfong; Dubot-Pérès, Audrey; Newton, Paul; Phangmanixay, Sommanikhone; Phongsavath, Khounthavy; Anh, Dang Duc; Quyen, Do; Hung, Tran Thi Mai; Thuy, Nguyen Thi Thu; Tan, Luong Minh; Pham, Anh Tuan; Hien, Nguyen; Huong, Do Thu; Hai, Le Thanh; Lam, Nguyen Van; An, Pham Nhat; Phuc, Phan Huu; Thuy, Phung Bich; Huong, Tran Thi Thu; Hlaing, Chaw Su; Aye, Aye Mya Min; Thair, Cho; Linn, Kyaw; July, May; Thein, Win; Kyaw, Latt Latt; Tin, Htay Htay; Tin, Ommar Swe; Oo, Khin Yi; Herrant, Magali; Lago, Magali; Seguy, Maud; Jouan, Marc; Hafner, Lukas; Pérot, Philippe; Eloit, Marc; Lortholary, Olivier; Capelle, Julien; Rosset, Bruno; Chevalier, Veronique; Honnorat, Jérôme; Pinto, Anne Laurie; Dubot-Peres, Auey; de Lamballerie, Xavier; Bleakley, Kevin; Murgue, Bernadette; Ferrant, Catherine; Devaux, Christian; Tissot-Dupont, Hervé; Moatti, Jean-Paul; Bonnet, Pascal; Fontenille, Didier; Delfraissy, Jean-François; Debré, Patrice; Durand, Benoit; Béziat, Vivien; Zhang, Peng; Rice, Charles; Hertzog, Paul |
| Contributors: |
Rockefeller University New York; King Abdulaziz City for Science and Technology Riyadh (KACST); Hudson Institute of Medical Research Clayton; Monash University Clayton; Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Hospital de Clínicas de Porto Alegre (HCPA); Universidade Federal do Rio Grande do Sul Porto Alegre – Brasil = Federal University of Rio Grande do Sul Porto Alegre – Brazil (UFRGS); Instituto Nacional de Genética Médica Populacional (INaGeMP); Hospital de Clínicas de Porto Alegre; Service des Maladies infectieuses et tropicales CHU Necker; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Biologie des Infections - Biology of Infection; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Necmettin Erbakan University Konya, Turquie; Bilkent University Ankara; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran Mexico (INCMNSZ); Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS); Institut Mondor de Recherche Biomédicale (IMRB); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor Créteil; IMRB - VHC/"Viruses-Hepatology-Cancers" Créteil (U955 Inserm - UPEC); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12); الجامعة اللبنانية بيروت = Lebanese University Beirut = Université libanaise Beyrouth (LU / ULB); Saint Georges Hospital University Medical Center Beirut; Agency for science, technology and research Singapore (A*STAR); Nanyang Technological University Singapour (NTU); University of Sharjah (UoS); King Saud University Riyadh (KSU); The University of Hong Kong (HKU); Aster CMI Hospital Bengaluru, India; Hadassah Hebrew University Medical Center Jerusalem; The Hebrew University of Jerusalem (HUJ); Mahidol University Bangkok; Instituto de Seguridad Social del Estado de México y Municipios Toluca, Mexico (ISSEMYM); Catholic University of Leuven = Katholieke Universiteit Leuven (KU Leuven); Centre International de Recherche en Infectiologie (CIRI); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Virology and human respiratory Pathologies - Virology and human respiratory Pathologies CIRI (CIRI-VirPath); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon); Statistique mathématique et apprentissage (CELESTE); Laboratoire de Mathématiques d'Orsay (LMO); Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Centre Inria de l'Université Paris-Saclay; Centre Inria de Saclay; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre Inria de Saclay; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria); Howard Hughes Medical Institute New York (HHMI); Howard Hughes Medical Institute (HHMI)-New York University School of Medicine; NYU System (NYU)-NYU System (NYU)-Rockefeller University New York -Columbia University Irving Medical Center (CUIMC); This study was supported in part by the St. Giles Foundation; the Rockefeller University; the Howard Hughes Medical Institute; Institut National de la Santé et de la Recherche Médicale (INSERM); the Imagine Institute; Paris Cité University; the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the National Center for Research Resources; the National Center for Advancing Sciences of the National Institutes of Health (NIH) (UL1TR001866); NIH (R01AI163029); American Lung Association (COVID-1026207); Stavros Niarchos Foundation (SNF) as part of its grant to the SNF Institute for Global Infectious Disease Research at The Rockefeller University; the Square Foundation; Grandir - Fonds de solidarité pour l’enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; the Battersea and Bowery Advisory Group; the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID); ANR GENVIR (ANR-20-CE93-003); ANR AAILC (ANR-21-LIBA-0002); ANR AI2D (ANR-22-CE15-0046); ANR GENFLU (ANR-22-CE92-0004); the ANR-RHU COVIFERON program (ANR-21-RHUS-08); the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 101057100 (UNDINE); the European Union’s Horizon 2020 research and innovation program under grant agreement No. 824110 (EASI-genomics); W.E. Ford, General Atlantic’s Chairman and Chief Executive Officer, G. Caillaux, General Atlantic’s Co-President, Managing Director and Head of Business in EMEA, and the General Atlantic Foundation; the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19); REACTing-INSERM. SEAe Consortium was supported by ANR SEA host factors (ANR-18-CE15-0020-01), Institut Pasteur, Institut Pasteur International Network, Fondation Mérieux, Aviesan Sud, INSERM, Wellcome Trust, Institut de Recherche pour le Développement (IRD), and Fondation Total. F. Al Qureshah was funded by the Ibn Rushd Postdoctoral Fellowship by King Abdullah University of Science and Technology (KAUST), and by the King Abdulaziz City for Science and Technology (KACST). P. Bastard was supported by the FRM (EA20170638020), the MD-PhD program of the Imagine Institute (with support from the Fondation Bettencourt-Schueller), and a “Poste CCA-INSERM-Bettencourt” (with support from the Fondation Bettencourt-Schueller). Y.L. Lau was supported by the Hong Kong Society for the Relief of Disabled Children for his research on inborn errors of immunity. R. Halwani was supported by the Deanship of Scientific Research, King Saud University, and funded through the Vice Deanship of Scientific Research Chairs; Research Chair of Prince Abdullah Ben Khalid Celiac Disease; Riyadh, Kingdom of Saudi Arabia. F. Vianna was supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (12960/2021-2). Open Access funding provided by Rockefeller University.; ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010); ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020); ANR-21-LIBA-0002,AAILC,Autoanticorps contre les interférons de type I chez les patients libanais hospitalisés pour COVID-19.(2021); ANR-22-CE15-0046,AI2D,Autoanticorps anti-interférons et maladies infectieuses associées(2022); ANR-22-CE92-0004,GENFLU,Rôle de la prédisposition génétique et les autoanticorps anti-IFN dans le développement des infections grippales sévères ?(2022); ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); ANR-18-CE15-0020,SEAe-HostFactors,Facteurs de susceptibilité de l'hôte à l'encéphalite pédiatrique en Asie du Sud Est(2018); European Project: 101057100,HORIZON-HLTH-2021-DISEASE-04,HORIZON-HLTH-2021-DISEASE-04,UNDINE(2022); European Project: 824110,H2020-INFRAIA-2018-2020,H2020-INFRAIA-2018-1,EASI-Genomics(2019) |
| Source: |
ISSN: 0022-1007. |
| Publisher Information: |
CCSD; Rockefeller University Press |
| Publication Year: |
2025 |
| Collection: |
Université Jean Monnet – Saint-Etienne: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39680367; info:eu-repo/grantAgreement//101057100/EU/The human genetic and immunological determinants of the clinical manifestations of SARS-CoV-2 infection: Towards personalised medicine/UNDINE; info:eu-repo/grantAgreement//824110/EU/European Advanced infraStructure for Innovative Genomics/EASI-Genomics; PUBMED: 39680367; PUBMEDCENTRAL: PMC11648951 |
| DOI: |
10.1084/jem.20241413 |
| Availability: |
https://hal.science/hal-04926027; https://hal.science/hal-04926027v1/document; https://hal.science/hal-04926027v1/file/jem_20241413.pdf; https://doi.org/10.1084/jem.20241413 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.94AA9266 |
| Database: |
BASE |