A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity

Al Qureshah, Fahd and Le Pen, Jérémie and de Weerd, Nicole A. and Moncada-Velez, Marcela and Materna, Marie and Lin, Daniel C. and Milisavljevic, Baptiste and Vianna, Fernanda and Bizien, Lucy and Lorenzo, Lazaro and Lecuit, Marc and Pommier, Jean-David and Keles, Sevgi and Ozcelik, Tayfun and Pedraza-Sanchez, Sigifredo and de Prost, Nicolas and El Zein, Loubna and Hammoud, Hassan and Ng, Lisa F.P. and Halwani, Rabih and Saheb Sharif-Askari, Narjes and Lau, Yu Lung and Tam, Anthony R. and Singh, Neha and Bhattad, Sagar and Berkun, Yackov and Chantratita, Wasun and Aguilar-López, Raúl and Shahrooei, Mohammad and Abel, Laurent and Aiuti, Alessandro and Al-Muhsen, Saleh and Alcántara-Garduño, Ana Bertha and Andreakos, Evangelos and Arias, Andrés A. and Feldman, Hagit Baris and Bastard, Paul and Bolze, Alexandre and Borghesi, Alessandro and Bousfiha, Ahmed A. and Brodin, Petter and Christodoulou, John and Cobat, Aurélie and Colobran, Roger and Condino-Neto, Antonio and Duvlis, Sotiriјa and Duval, Xavier and Dündar, Munis and Fakhreddine, Soha and Fellay, Jacques and Flores, Carlos and Franco, José Luis and Gorochov, Guy and Gregersen, Peter K. and Hagin, David and Halwani, Rabih and Herrera, María Teresa and Hung, Ivan Fan-Ngai and Jouanguy, Emmanuelle and Lau, Yu-Lung and Leung, Daniel and Le-voyer, Tom and Mansouri, Davood and Mercado-García, Jesús and Meyts, Isabelle and Mogensen, Trine H. and Ng, Lisa F.P. and Novelli, Antonio and Novelli, Giuseppe and Okada, Satoshi and Ozcelik, Firat and Ozcelik, Tayfun and de Diego, Rebeca Perez and Perez-Tur, Jordi and Pesole, Graziano and Puel, Anne and Renia, Laurent and Resnick, Igor and Rodríguez-Gallego, Carlos and Sbeity, Manal and Sedighzadeh, Sahar and Shahrooei, Mohammad and Soler-Palacín, Pere and Spaan, András N. and Tangye, Stuart G. and Tayoun, Ahmad Abou and Temel, Şehime Gülsün and Thorball, Christian and Torktaz, Ibrahim and Trouillet-Assant, Sophie and Turvey, Stuart E. and Uddin, Furkan and Vianna, Fernanda Sales Luiz and Vinh, Donald C. and Zabaleta-Martínez, Oscar and Zhang, Qian and Zhang, Shen-Ying and Casanova, Jean-Laurent and Eng, Chanreaksmey and Bun, Kimrong and Oum, MengHeng and Piola, Patrice and Tarantola, Arnaud and Channa, Mey and Duong, Veasna and Buchy, Philippe and Gorman, Chris and Pommier, Jean-David and Crabol, Yoann and Dussart, Philippe and Bunleat, M. and Panha, M. and Sim, M.Kanarith and Bunnakea, Em and Laurent, Denis and Sothy, Heng and Santy, Ky and Douangnouvong, Anousone and Chommanam, Danoy and Phakhounthong, Khansoudaphone and Vongsouvath, Manivanh and Seephone, Malee and Sibounheunang, Bountoy and Rattanavong, Sayaphet and Davong, Viengmon and Vongsouvath, Malavanh and Mayxay, Mayfong and Dubot-Pérès, Audrey and Newton, Paul N. and Phangmanixay, Sommanikhone and Phongsavath, Khounthavy and Anh, Dang Duc and Quyen, Do and Hung, Tran Thi Mai and Thuy, Nguyen Thi Thu and Tan, Luong Minh and Pham, Anh Tuan and Hien, Nguyen and Huong, Do Thu and Hai, Le Thanh and Lam, Nguyen Van and An, Pham Nhat and Phuc, Phan Huu and Thuy, Phung Bich and Huong, Tran Thi Thu and Hlaing, Chaw Su and Aye, Aye Mya Min and Thair, Cho and Linn, Kyaw and July, May and Thein, Win and Kyaw, Latt Latt and Tin, Htay Htay and Tin, Ommar Swe and Oo, Khin Yi and Crabol, Yoann and Herrant, Magali and Lago, Magali and Seguy, Maud and Jouan, Marc and Hafner, Lukas and Pérot, Philippe and Eloit, Marc and Lecuit, Marc and Lortholary, Olivier and Capelle, Julien and Rosset, Bruno and Chevalier, Veronique and Honnorat, Jérôme and Pinto, Anne Laurie and Dubot-Peres, Auey and de Lamballerie, Xavier and Bleakley, Kevin and Murgue, Bernadette and Ferrant, Catherine and Devaux, Christian and Tissot-Dupont, Hervé and Moatti, Jean-Paul and Mayxay, Mayfong and Bonnet, Pascal and Fontenille, Didier and Delfraissy, Jean-François and Debré, Patrice and Durand, Benoit and Abel, Laurent and Bastard, Paul and Jouanguy, Emmanuelle and Béziat, Vivien and Zhang, Peng and Rice, Charles M. and Cobat, Aurélie and Zhang, Shen-Ying and Hertzog, Paul J. and Casanova, Jean-Laurent and Zhang, Qian (2025) A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity. Journal of Experimental Medicine, 222 (2). ISSN 0022-1007

[thumbnail of jem_20241413.pdf] Text
jem_20241413.pdf
Download (7MB)

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.

Item Type: Article
Subjects: Medical and Health Sciences > Basic medicine
Medical and Health Sciences > Health sciences
Divisions: Faculty of Medical Science
Depositing User: Sotirija Duvlis
Date Deposited: 06 Feb 2025 10:33
Last Modified: 06 Feb 2025 13:26
URI: https://eprints.ugd.edu.mk/id/eprint/35661

Actions (login required)

View Item
View Item