A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity
Authors: Fahd Al Qureshah, Jérémie Le Pen, Nicole A. de Weerd, Marcela Moncada-Velez, Marie Materna, Daniel C. Lin, Baptiste Milisavljevic, Fernanda Vianna, Lucy Bizien, Lazaro Lorenzo, Marc Lecuit, Jean-David Pommier, Sevgi Keles, Tayfun Ozcelik, Sigifredo Pedraza-Sanchez, Nicolas de Prost, Loubna El Zein, Hassan Hammoud, Lisa F.P. Ng, Rabih Halwani, Narjes Saheb Sharif-Askari, Yu Lung Lau, Anthony R. Tam, Neha Singh, Sagar Bhattad, Yackov Berkun, Wasun Chantratita, Raúl Aguilar-López, Mohammad Shahrooei, Laurent Abel, Alessandro Aiuti, Saleh Al-Muhsen, Ana Bertha Alcántara-Garduño, Evangelos Andreakos, Andrés A. Arias, Hagit Baris Feldman, Paul Bastard, Alexandre Bolze, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, John Christodoulou, Aurélie Cobat, Roger Colobran, Antonio Condino-Neto, Sotiriјa Duvlis, Xavier Duval, Munis Dündar, Soha Fakhreddine, Jacques Fellay, Carlos Flores, José Luis Franco, Guy Gorochov, Peter K. Gregersen, David Hagin, Rabih Halwani, María Teresa Herrera, Ivan Fan-Ngai Hung, Emmanuelle Jouanguy, Yu-Lung Lau, Daniel Leung, Tom Le-voyer, Davood Mansouri, Jesús Mercado-García, Isabelle Meyts, Trine H. Mogensen, Lisa F.P. Ng, Antonio Novelli, Giuseppe Novelli, Satoshi Okada, Firat Ozcelik, Tayfun Ozcelik, Rebeca Perez de Diego, Jordi Perez-Tur, Graziano Pesole, Anne Puel, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Manal Sbeity, Sahar Sedighzadeh, Mohammad Shahrooei, Pere Soler-Palacín, András N. Spaan, Stuart G. Tangye, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Ibrahim Torktaz, Sophie Trouillet-Assant, Stuart E. Turvey, Furkan Uddin, Fernanda Sales Luiz Vianna, Donald C. Vinh, Oscar Zabaleta-Martínez, Qian Zhang, Shen-Ying Zhang, Jean-Laurent Casanova, Chanreaksmey Eng, Kimrong Bun, MengHeng Oum, Patrice Piola, Arnaud Tarantola, Mey Channa, Veasna Duong, Philippe Buchy, Chris Gorman, Jean-David Pommier, Yoann Crabol, Philippe Dussart, M. Bunleat, M. Panha, M.Kanarith Sim, Em Bunnakea, Denis Laurent, Heng Sothy, Ky Santy, Anousone Douangnouvong, Danoy Chommanam, Khansoudaphone Phakhounthong, Manivanh Vongsouvath, Malee Seephone, Bountoy Sibounheunang, Sayaphet Rattanavong, Viengmon Davong, Malavanh Vongsouvath, Mayfong Mayxay, Audrey Dubot-Pérès, Paul N. Newton, Sommanikhone Phangmanixay, Khounthavy Phongsavath, Dang Duc Anh, Do Quyen, Tran Thi Mai Hung, Nguyen Thi Thu Thuy, Luong Minh Tan, Anh Tuan Pham, Nguyen Hien, Do Thu Huong, Le Thanh Hai, Nguyen Van Lam, Pham Nhat An, Phan Huu Phuc, Phung Bich Thuy, Tran Thi Thu Huong, Chaw Su Hlaing, Aye Mya Min Aye, Cho Thair, Kyaw Linn, May July, Win Thein, Latt Latt Kyaw, Htay Htay Tin, Ommar Swe Tin, Khin Yi Oo, Yoann Crabol, Magali Herrant, Magali Lago, Maud Seguy, Marc Jouan, Lukas Hafner, Philippe Pérot, Marc Eloit, Marc Lecuit, Olivier Lortholary, Julien Capelle, Bruno Rosset, Veronique Chevalier, Jérôme Honnorat, Anne Laurie Pinto, Auey Dubot-Peres, Xavier de Lamballerie, Kevin Bleakley, Bernadette Murgue, Catherine Ferrant, Christian Devaux, Hervé Tissot-Dupont, Jean-Paul Moatti, Mayfong Mayxay, Pascal Bonnet, Didier Fontenille, Jean-François Delfraissy, Patrice Debré, Benoit Durand, Laurent Abel, Paul Bastard, Emmanuelle Jouanguy, Vivien Béziat, Peng Zhang, Charles M. Rice, Aurélie Cobat, Shen-Ying Zhang, Paul J. Hertzog, Jean-Laurent Casanova, Qian Zhang
Journal: The Journal of Experimental Medicine (2024)

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.