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

Fahd Al Qureshah; Jérémie Le Pen; Nicole A. de Weerd; Marcela Moncada-Velez; Marie Materna; Danielc 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; Paul Bastard; Emmanuelle Jouanguy; Vivien Béziat; Peng Zhang; Charles M Rice; Aurélie Cobat; Shen Ying Zhang; Paul J. Hertzog; Jean Laurent Casanova; Qian Zhang; Alessandro Aiuti; Saleh Al-Muhsen; Ana Bertha Alcántara-Garduño; Evangelos Andreakos; Andrés A. Arias; Hagit Baris Feldman; Alexandre Bolze; Alessandro Borghesi; Ahmed A. Bousfiha; Petter Brodin; John Christodoulou; 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; 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; 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; K. M. Furkan Uddin; Fernanda Sales Luiz Vianna; Donald C. Vinh; Oscar Zabaleta-Martínez; Chanreaksmey Eng; Kimrong Bun; Mr Mengheng Oum; Patrice Piola; Arnaud Tarantola; Mey Channa; Veasna Duong; Philippe Buchy; Chris Gorman; 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; Mr Do Quyen; Tran Thi Mai Hung; Nguyen Thi Thu Thuy; Mr 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; Committee 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

doi:10.1084/jem.20241413

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

Fahd Al Qureshah^*, Jérémie Le Pen, Nicole A. de Weerd, Marcela Moncada-Velez, Marie Materna, Danielc 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 HalwaniNarjes Saheb Sharif-Askari, Yu Lung Lau, Anthony R. Tam, Neha Singh, Sagar Bhattad, Yackov Berkun, Wasun Chantratita, Raúl Aguilar-López, Mohammad Shahrooei, 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^*, Alessandro Aiuti, Saleh Al-Muhsen, Ana Bertha Alcántara-Garduño, Evangelos Andreakos, Andrés A. Arias, Hagit Baris Feldman, Alexandre Bolze, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, John Christodoulou, 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, 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, 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, K. M. Furkan Uddin, Fernanda Sales Luiz Vianna, Donald C. Vinh, Oscar Zabaleta-Martínez, Chanreaksmey Eng, Kimrong Bun, Mr Mengheng Oum, Patrice Piola, Arnaud Tarantola, Mey Channa, Veasna Duong, Philippe Buchy, Chris Gorman, 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, Mr Do Quyen, Tran Thi Mai Hung, Nguyen Thi Thu Thuy, Mr 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, Committee 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	e20241413
Journal	Journal of Experimental Medicine
Volume	222
Issue number	2
DOIs	https://doi.org/10.1084/jem.20241413
Publication status	Published - 3 Feb 2025

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10.1084/jem.20241413Licence: CC BY

jem_20241413Final published version, 7.12 MBLicence: CC BY

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Al Qureshah, F., Le Pen, J., de Weerd, N. A., Moncada-Velez, M., Materna, M., Lin, D., 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., F P Ng, L., ... Durand, B. (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), Article e20241413. https://doi.org/10.1084/jem.20241413

@article{a29c7de7307747d79e4a4fb8675ad6f8,

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

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.",

author = "\{Al Qureshah\}, Fahd and \{Le Pen\}, J{\'e}r{\'e}mie and \{de Weerd\}, \{Nicole A.\} and Marcela Moncada-Velez and Marie Materna and Danielc Lin and Baptiste Milisavljevic and Fernanda Vianna and Lucy Bizien and Lazaro Lorenzo and Marc Lecuit and Pommier, \{Jean David\} and Sevgi Keles and Tayfun Ozcelik and Sigifredo Pedraza-Sanchez and \{de Prost\}, Nicolas and \{El Zein\}, Loubna and Hassan Hammoud and \{F P Ng\}, Lisa and Rabih Halwani and Sharif-Askari, \{Narjes Saheb\} and Lau, \{Yu Lung\} and Tam, \{Anthony R.\} and Neha Singh and Sagar Bhattad and Yackov Berkun and Wasun Chantratita and Ra{\'u}l Aguilar-L{\'o}pez and Mohammad Shahrooei and Laurent Abel and Paul Bastard and Emmanuelle Jouanguy and Vivien B{\'e}ziat and Peng Zhang and \{M Rice\}, Charles and Aur{\'e}lie Cobat and Zhang, \{Shen Ying\} and Hertzog, \{Paul J.\} and Casanova, \{Jean Laurent\} and Qian Zhang and Alessandro Aiuti and Saleh Al-Muhsen and Alc{\'a}ntara-Gardu{\~n}o, \{Ana Bertha\} and Evangelos Andreakos and Arias, \{Andr{\'e}s A.\} and Feldman, \{Hagit Baris\} and Alexandre Bolze and Alessandro Borghesi and Bousfiha, \{Ahmed A.\} and Petter Brodin and John Christodoulou and Roger Colobran and Antonio Condino-Neto and Sotiriјa Duvlis and Xavier Duval and Munis D{\"u}ndar and Soha Fakhreddine and Jacques Fellay and Carlos Flores and Franco, \{Jos{\'e} Luis\} and Guy Gorochov and Gregersen, \{Peter K.\} and David Hagin and Rabih Halwani and Herrera, \{Mar{\'i}a Teresa\} and Hung, \{Ivan Fan Ngai\} and Lau, \{Yu Lung\} and Daniel Leung and Tom Le-Voyer and Davood Mansouri and Jes{\'u}s Mercado-Garc{\'i}a and Isabelle Meyts and Mogensen, \{Trine H.\} and Ng, \{Lisa F.P.\} and Antonio Novelli and Giuseppe Novelli and Satoshi Okada and Firat Ozcelik and \{de Diego\}, \{Rebeca Perez\} and Jordi Perez-Tur and Graziano Pesole and Anne Puel and Laurent Renia and Igor Resnick and Carlos Rodr{\'i}guez-Gallego and Manal Sbeity and Sahar Sedighzadeh and Mohammad Shahrooei and Pere Soler-Palac{\'i}n and Spaan, \{Andr{\'a}s N.\} and Tangye, \{Stuart G.\} and Tayoun, \{Ahmad Abou\} and Temel, \{{\c S}ehime G{\"u}ls{\"u}n\} and Christian Thorball and Ibrahim Torktaz and Sophie Trouillet-Assant and Turvey, \{Stuart E.\} and \{Furkan Uddin\}, \{K. M.\} and \{Luiz Vianna\}, \{Fernanda Sales\} and Vinh, \{Donald C.\} and Oscar Zabaleta-Mart{\'i}nez and Chanreaksmey Eng and Kimrong Bun and \{Mengheng Oum\}, Mr and Patrice Piola and Arnaud Tarantola and Mey Channa and Veasna Duong and Philippe Buchy and Chris Gorman and Yoann Crabol and Philippe Dussart and M. Bunleat and M. Panha and \{Kanarith Sim\}, M. and Em Bunnakea and Denis Laurent and Heng Sothy and Ky Santy and Anousone Douangnouvong and Danoy Chommanam and Khansoudaphone Phakhounthong and Manivanh Vongsouvath and Malee Seephone and Bountoy Sibounheunang and Sayaphet Rattanavong and Viengmon Davong and Malavanh Vongsouvath and Mayfong Mayxay and Audrey Dubot-P{\'e}r{\`e}s and Newton, \{Paul N.\} and Sommanikhone Phangmanixay and Khounthavy Phongsavath and \{Duc Anh\}, Dang and \{Do Quyen\}, Mr and \{Mai Hung\}, \{Tran Thi\} and \{Thu Thuy\}, \{Nguyen Thi\} and \{Minh Tan\}, \{Mr Luong\} and Pham, \{Anh Tuan\} and Nguyen Hien 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 \{Thu Huong\}, \{Tran Thi\} and Hlaing, \{Chaw Su\} and \{Min Aye\}, \{Aye Mya\} and Cho Thair and Kyaw Linn and May July and Win Thein and Kyaw, \{Latt Latt\} and Tin, \{Htay Htay\} and Tin, \{Ommar Swe\} and Oo, \{Khin Yi\} and Yoann Crabol and Magali Herrant and Magali Lago and Maud Seguy and Marc Jouan and Lukas Hafner and Philippe P{\'e}rot and Marc Eloit and Marc Lecuit and Olivier Lortholary and Julien Capelle and Bruno Rosset and Veronique Chevalier and J{\'e}r{\^o}me Honnorat and Pinto, \{Anne Laurie\} and Auey Dubot-Peres and \{de Lamballerie\}, Xavier and Kevin Bleakley and Murgue, \{Committee Bernadette\} and Catherine Ferrant and Christian Devaux and Herv{\'e} Tissot-Dupont and Moatti, \{Jean Paul\} and Mayfong Mayxay and Pascal Bonnet and Didier Fontenille and Delfraissy, \{Jean Fran{\c c}ois\} and Patrice Debr{\'e} and Benoit Durand",

note = "Publisher Copyright: {\textcopyright} 2024 Al Qureshah et al.",

year = "2025",

month = feb,

day = "3",

doi = "10.1084/jem.20241413",

language = "English",

volume = "222",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "2",

}

Al Qureshah, F, Le Pen, J, de Weerd, NA, Moncada-Velez, M, Materna, M, Lin, D, Milisavljevic, B, Vianna, F, Bizien, L, Lorenzo, L, Lecuit, M, Pommier, JD, Keles, S, Ozcelik, T, Pedraza-Sanchez, S, de Prost, N, El Zein, L, Hammoud, H, F P Ng, L, Halwani, R, Sharif-Askari, NS, Lau, YL, Tam, AR, Singh, N, Bhattad, S, Berkun, Y, Chantratita, W, Aguilar-López, R, Shahrooei, M, Abel, L, Bastard, P, Jouanguy, E, Béziat, V, Zhang, P, M Rice, C, Cobat, A, Zhang, SY, Hertzog, PJ, Casanova, JL, Zhang, Q, Aiuti, A, Al-Muhsen, S, Alcántara-Garduño, AB, Andreakos, E, Arias, AA, Feldman, HB, Bolze, A, Borghesi, A, Bousfiha, AA, Brodin, P, Christodoulou, J, Colobran, R, Condino-Neto, A, Duvlis, S, Duval, X, Dündar, M, Fakhreddine, S, Fellay, J, Flores, C, Franco, JL, Gorochov, G, Gregersen, PK, Hagin, D, Halwani, R, Herrera, MT, Hung, IFN, Lau, YL, Leung, D, Le-Voyer, T, Mansouri, D, Mercado-García, J, Meyts, I, Mogensen, TH, Ng, LFP, Novelli, A, Novelli, G, Okada, S, Ozcelik, F, de Diego, RP, Perez-Tur, J, Pesole, G, Puel, A, Renia, L, Resnick, I, Rodríguez-Gallego, C, Sbeity, M, Sedighzadeh, S, Shahrooei, M, Soler-Palacín, P, Spaan, AN, Tangye, SG, Tayoun, AA, Temel, ŞG, Thorball, C, Torktaz, I, Trouillet-Assant, S, Turvey, SE, Furkan Uddin, KM, Luiz Vianna, FS, Vinh, DC, Zabaleta-Martínez, O, Eng, C, Bun, K, Mengheng Oum, M, Piola, P, Tarantola, A, Channa, M, Duong, V, Buchy, P, Gorman, C, Crabol, Y, Dussart, P, Bunleat, M, Panha, M, Kanarith Sim, M, Bunnakea, E, Laurent, D, Sothy, H, Santy, K, Douangnouvong, A, Chommanam, D, Phakhounthong, K, Vongsouvath, M, Seephone, M, Sibounheunang, B, Rattanavong, S, Davong, V, Vongsouvath, M, Mayxay, M, Dubot-Pérès, A, Newton, PN, Phangmanixay, S, Phongsavath, K, Duc Anh, D, Do Quyen, M, Mai Hung, TT, Thu Thuy, NT, Minh Tan, ML, Pham, AT, Hien, N, Huong, DT, Hai, LT, Lam, NV, An, PN, Phuc, PH, Thuy, PB, Thu Huong, TT, Hlaing, CS, Min Aye, AM, Thair, C, Linn, K, July, M, Thein, W, Kyaw, LL, Tin, HH, Tin, OS, Oo, KY, Crabol, Y, Herrant, M, Lago, M, Seguy, M, Jouan, M, Hafner, L, Pérot, P, Eloit, M, Lecuit, M, Lortholary, O, Capelle, J, Rosset, B, Chevalier, V, Honnorat, J, Pinto, AL, Dubot-Peres, A, de Lamballerie, X, Bleakley, K, Murgue, CB, Ferrant, C, Devaux, C, Tissot-Dupont, H, Moatti, JP, Mayxay, M, Bonnet, P, Fontenille, D, Delfraissy, JF, Debré, P & Durand, B 2025, 'A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity', Journal of Experimental Medicine, vol. 222, no. 2, e20241413. https://doi.org/10.1084/jem.20241413

TY - JOUR

T1 - A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity

AU - Al Qureshah, Fahd

AU - Le Pen, Jérémie

AU - de Weerd, Nicole A.

AU - Moncada-Velez, Marcela

AU - Materna, Marie

AU - Lin, Danielc

AU - Milisavljevic, Baptiste

AU - Vianna, Fernanda

AU - Bizien, Lucy

AU - Lorenzo, Lazaro

AU - Lecuit, Marc

AU - Pommier, Jean David

AU - Keles, Sevgi

AU - Ozcelik, Tayfun

AU - Pedraza-Sanchez, Sigifredo

AU - de Prost, Nicolas

AU - El Zein, Loubna

AU - Hammoud, Hassan

AU - F P Ng, Lisa

AU - Halwani, Rabih

AU - Sharif-Askari, Narjes Saheb

AU - Lau, Yu Lung

AU - Tam, Anthony R.

AU - Singh, Neha

AU - Bhattad, Sagar

AU - Berkun, Yackov

AU - Chantratita, Wasun

AU - Aguilar-López, Raúl

AU - Shahrooei, Mohammad

AU - Abel, Laurent

AU - Bastard, Paul

AU - Jouanguy, Emmanuelle

AU - Béziat, Vivien

AU - Zhang, Peng

AU - M Rice, Charles

AU - Cobat, Aurélie

AU - Zhang, Shen Ying

AU - Hertzog, Paul J.

AU - Casanova, Jean Laurent

AU - Zhang, Qian

AU - Aiuti, Alessandro

AU - Al-Muhsen, Saleh

AU - Alcántara-Garduño, Ana Bertha

AU - Andreakos, Evangelos

AU - Arias, Andrés A.

AU - Feldman, Hagit Baris

AU - Bolze, Alexandre

AU - Borghesi, Alessandro

AU - Bousfiha, Ahmed A.

AU - Brodin, Petter

AU - Christodoulou, John

AU - Colobran, Roger

AU - Condino-Neto, Antonio

AU - Duvlis, Sotiriјa

AU - Duval, Xavier

AU - Dündar, Munis

AU - Fakhreddine, Soha

AU - Fellay, Jacques

AU - Flores, Carlos

AU - Franco, José Luis

AU - Gorochov, Guy

AU - Gregersen, Peter K.

AU - Hagin, David

AU - Halwani, Rabih

AU - Herrera, María Teresa

AU - Hung, Ivan Fan Ngai

AU - Lau, Yu Lung

AU - Leung, Daniel

AU - Le-Voyer, Tom

AU - Mansouri, Davood

AU - Mercado-García, Jesús

AU - Meyts, Isabelle

AU - Mogensen, Trine H.

AU - Ng, Lisa F.P.

AU - Novelli, Antonio

AU - Novelli, Giuseppe

AU - Okada, Satoshi

AU - Ozcelik, Firat

AU - de Diego, Rebeca Perez

AU - Perez-Tur, Jordi

AU - Pesole, Graziano

AU - Puel, Anne

AU - Renia, Laurent

AU - Resnick, Igor

AU - Rodríguez-Gallego, Carlos

AU - Sbeity, Manal

AU - Sedighzadeh, Sahar

AU - Shahrooei, Mohammad

AU - Soler-Palacín, Pere

AU - Spaan, András N.

AU - Tangye, Stuart G.

AU - Tayoun, Ahmad Abou

AU - Temel, Şehime Gülsün

AU - Thorball, Christian

AU - Torktaz, Ibrahim

AU - Trouillet-Assant, Sophie

AU - Turvey, Stuart E.

AU - Furkan Uddin, K. M.

AU - Luiz Vianna, Fernanda Sales

AU - Vinh, Donald C.

AU - Zabaleta-Martínez, Oscar

AU - Eng, Chanreaksmey

AU - Bun, Kimrong

AU - Mengheng Oum, Mr

AU - Piola, Patrice

AU - Tarantola, Arnaud

AU - Channa, Mey

AU - Duong, Veasna

AU - Buchy, Philippe

AU - Gorman, Chris

AU - Crabol, Yoann

AU - Dussart, Philippe

AU - Bunleat, M.

AU - Panha, M.

AU - Kanarith Sim, M.

AU - Bunnakea, Em

AU - Laurent, Denis

AU - Sothy, Heng

AU - Santy, Ky

AU - Douangnouvong, Anousone

AU - Chommanam, Danoy

AU - Phakhounthong, Khansoudaphone

AU - Vongsouvath, Manivanh

AU - Seephone, Malee

AU - Sibounheunang, Bountoy

AU - Rattanavong, Sayaphet

AU - Davong, Viengmon

AU - Vongsouvath, Malavanh

AU - Mayxay, Mayfong

AU - Dubot-Pérès, Audrey

AU - Newton, Paul N.

AU - Phangmanixay, Sommanikhone

AU - Phongsavath, Khounthavy

AU - Duc Anh, Dang

AU - Do Quyen, Mr

AU - Mai Hung, Tran Thi

AU - Thu Thuy, Nguyen Thi

AU - Minh Tan, Mr Luong

AU - Pham, Anh Tuan

AU - Hien, Nguyen

AU - Huong, Do Thu

AU - Hai, Le Thanh

AU - Lam, Nguyen Van

AU - An, Pham Nhat

AU - Phuc, Phan Huu

AU - Thuy, Phung Bich

AU - Thu Huong, Tran Thi

AU - Hlaing, Chaw Su

AU - Min Aye, Aye Mya

AU - Thair, Cho

AU - Linn, Kyaw

AU - July, May

AU - Thein, Win

AU - Kyaw, Latt Latt

AU - Tin, Htay Htay

AU - Tin, Ommar Swe

AU - Oo, Khin Yi

AU - Crabol, Yoann

AU - Herrant, Magali

AU - Lago, Magali

AU - Seguy, Maud

AU - Jouan, Marc

AU - Hafner, Lukas

AU - Pérot, Philippe

AU - Eloit, Marc

AU - Lecuit, Marc

AU - Lortholary, Olivier

AU - Capelle, Julien

AU - Rosset, Bruno

AU - Chevalier, Veronique

AU - Honnorat, Jérôme

AU - Pinto, Anne Laurie

AU - Dubot-Peres, Auey

AU - de Lamballerie, Xavier

AU - Bleakley, Kevin

AU - Murgue, Committee Bernadette

AU - Ferrant, Catherine

AU - Devaux, Christian

AU - Tissot-Dupont, Hervé

AU - Moatti, Jean Paul

AU - Mayxay, Mayfong

AU - Bonnet, Pascal

AU - Fontenille, Didier

AU - Delfraissy, Jean François

AU - Debré, Patrice

AU - Durand, Benoit

PY - 2025/2/3

Y1 - 2025/2/3

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85212991529

U2 - 10.1084/jem.20241413

DO - 10.1084/jem.20241413

M3 - Article

C2 - 39680367

AN - SCOPUS:85212991529

SN - 0022-1007

VL - 222

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 2

M1 - e20241413

ER -

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

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