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1. Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Author

Matuozzo, Daniela, Talouarn, Estelle, Marchal, Astrid, Zhang, Peng, Manry, Jeremy, Seeleuthner, Yoann, Zhang, Yu, Bolze, Alexandre, Chaldebas, Matthieu, Milisavljevic, Baptiste, Gervais, Adrian, Bastard, Paul, Asano, Takaki, Bizien, Lucy, Barzaghi, Federica, Abolhassani, Hassan, Tayoun, Ahmad Abou, Aiuti, Alessandro, Darazam, Ilad Alavi, Allende, Luis M., Alonso-Arias, Rebeca, Arias, Andrés Augusto, Aytekin, Gokhan, Bergman, Peter, Bondesan, Simone, Bryceson, Yenan T., Bustos, Ingrid G., Cabrera-Marante, Oscar, Carcel, Sheila, Carrera, Paola, Casari, Giorgio, Chaïbi, Khalil, Colobran, Roger, Condino-Neto, Antonio, Covill, Laura E., Delmonte, Ottavia M., Zein, Loubna El, Flores, Carlos, Gregersen, Peter K., Gut, Marta, Haerynck, Filomeen, Halwani, Rabih, Hancerli, Selda, Hammarström, Lennart, Hatipoğlu, Nevin, Karbuz, Adem, Keles, Sevgi, Kyheng, Christèle, Leon-Lopez, Rafael, Franco, Jose Luis, Mansouri, Davood, Martinez-Picado, Javier, Akcan, Ozge Metin, Migeotte, Isabelle, Morange, Pierre-Emmanuel, Morelle, Guillaume, Martin-Nalda, Andrea, Novelli, Giuseppe, Novelli, Antonio, Ozcelik, Tayfun, Palabiyik, Figen, Pan-Hammarström, Qiang, de Diego, Rebeca Pérez, Planas-Serra, Laura, Pleguezuelo, Daniel E., Prando, Carolina, Pujol, Aurora, Reyes, Luis Felipe, Rivière, Jacques G., Rodriguez-Gallego, Carlos, Rojas, Julian, Rovere-Querini, Patrizia, Schlüter, Agatha, Shahrooei, Mohammad, Sobh, Ali, Soler-Palacin, Pere, Tandjaoui-Lambiotte, Yacine, Tipu, Imran, Tresoldi, Cristina, Troya, Jesus, van de Beek, Diederik, Zatz, Mayana, Zawadzki, Pawel, Al-Muhsen, Saleh Zaid, Alosaimi, Mohammed Faraj, Alsohime, Fahad M., Baris-Feldman, Hagit, Butte, Manish J., Constantinescu, Stefan N., Cooper, Megan A., Dalgard, Clifton L., Fellay, Jacques, Heath, James R., Lau, Yu-Lung, Lifton, Richard P., Maniatis, Tom, Mogensen, Trine H., von Bernuth, Horst, Lermine, Alban, Vidaud, Michel, Boland, Anne, Deleuze, Jean-François, Nussbaum, Robert, Kahn-Kirby, Amanda, Mentre, France, Tubiana, Sarah, Gorochov, Guy, Tubach, Florence, Hausfater, Pierre, Meyts, Isabelle, Zhang, Shen-Ying, Puel, Anne, Notarangelo, Luigi D., Boisson-Dupuis, Stephanie, Su, Helen C., Boisson, Bertrand, Jouanguy, Emmanuelle, Casanova, Jean-Laurent, Zhang, Qian, Abel, Laurent, and Cobat, Aurélie

Published
2024
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2. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Author

Matuozzo, Daniela, Talouarn, Estelle, Marchal, Astrid, Zhang, Peng, Manry, Jeremy, Seeleuthner, Yoann, Zhang, Yu, Bolze, Alexandre, Chaldebas, Matthieu, Milisavljevic, Baptiste, Gervais, Adrian, Bastard, Paul, Asano, Takaki, Bizien, Lucy, Barzaghi, Federica, Abolhassani, Hassan, Abou Tayoun, Ahmad, Aiuti, Alessandro, Alavi Darazam, Ilad, Allende, Luis M, Alonso-Arias, Rebeca, Arias, Andrés Augusto, Aytekin, Gokhan, Bergman, Peter, Bondesan, Simone, Bryceson, Yenan T, Bustos, Ingrid G, Cabrera-Marante, Oscar, Carcel, Sheila, Carrera, Paola, Casari, Giorgio, Chaïbi, Khalil, Colobran, Roger, Condino-Neto, Antonio, Covill, Laura E, Delmonte, Ottavia M, El Zein, Loubna, Flores, Carlos, Gregersen, Peter K, Gut, Marta, Haerynck, Filomeen, Halwani, Rabih, Hancerli, Selda, Hammarström, Lennart, Hatipoğlu, Nevin, Karbuz, Adem, Keles, Sevgi, Kyheng, Christèle, Leon-Lopez, Rafael, Franco, Jose Luis, Mansouri, Davood, Martinez-Picado, Javier, Metin Akcan, Ozge, Migeotte, Isabelle, Morange, Pierre-Emmanuel, Morelle, Guillaume, Martin-Nalda, Andrea, Novelli, Giuseppe, Novelli, Antonio, Ozcelik, Tayfun, Palabiyik, Figen, Pan-Hammarström, Qiang, de Diego, Rebeca Pérez, Planas-Serra, Laura, Pleguezuelo, Daniel E, Prando, Carolina, Pujol, Aurora, Reyes, Luis Felipe, Rivière, Jacques G, Rodriguez-Gallego, Carlos, Rojas, Julian, Rovere-Querini, Patrizia, Schlüter, Agatha, Shahrooei, Mohammad, Sobh, Ali, Soler-Palacin, Pere, Tandjaoui-Lambiotte, Yacine, Tipu, Imran, Tresoldi, Cristina, Troya, Jesus, van de Beek, Diederik, Zatz, Mayana, Zawadzki, Pawel, Al-Muhsen, Saleh Zaid, Alosaimi, Mohammed Faraj, Alsohime, Fahad M, Baris-Feldman, Hagit, Butte, Manish J, Constantinescu, Stefan N, Cooper, Megan A, Dalgard, Clifton L, Fellay, Jacques, Heath, James R, Lau, Yu-Lung, Lifton, Richard P, Maniatis, Tom, Mogensen, Trine H, von Bernuth, Horst, Lermine, Alban, and Vidaud, Michel

Subjects
Clinical Research, Infectious Diseases, Pneumonia & Influenza, Genetics, Human Genome, Prevention, 2.1 Biological and endogenous factors, Aetiology, Humans, Young Adult, Adult, Middle Aged, COVID-19, SARS-CoV-2, Toll-Like Receptor 3, Toll-Like Receptor 7, Interferon Type I, Autoantibodies, COVID Human Genetic Effort, COVIDeF Study Group, French COVID Cohort Study Group, CoV-Contact Cohort, COVID-STORM Clinicians, COVID Clinicians, Orchestra Working Group, Amsterdam UMC Covid-19 Biobank, NIAID-USUHS COVID Study Group, Immunity, Rare variants, Type I interferon, Clinical Sciences
Abstract

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10-5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Published
2023

3. The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Author

Manry, Jérémy, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Liis, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesús, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G., Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B., Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Mégarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R., Franco, José Luis, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M., Zhang, Yu, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Anglicheau, Dany, Planas, Anna M., Haerynck, Filomeen, Duvlis, Sotirija, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A., Bakkouri, Jalila El, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N., Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A., Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G., Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli Y., Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C., Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H., Kennelly, Sean P., Bourke, Nollaig M., Halwani, Rabih, Sharif-Askari, Fatemeh Saheb, Dorgham, Karim, Sallette, Jérôme, Sedkaoui, Souad Mehlal, AlKhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C., Erikstrup, Christian, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András N., Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard P., Mane, Shrikant, Anderson, Mark S., Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H., Rowen, Lee, Mond, James, Debette, Stéphanie, de Lamballerie, Xavier, Burdet, Charles, Bouadma, Lila, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K., Piemonti, Lorenzo, Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M., Tiberghien, Pierre, Zhang, Qian, Casanova, Jean-Laurent, Abel, Laurent, and Cobat, Aurélie

Published
2022

4. Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

Author

Rosain, Jérémie, Neehus, Anna-Lena, Manry, Jérémy, Yang, Rui, Le Pen, Jérémie, Daher, Wassim, Liu, Zhiyong, Chan, Yi-Hao, Tahuil, Natalia, Türel, Özden, Bourgey, Mathieu, Ogishi, Masato, Doisne, Jean-Marc, Izquierdo, Helena M., Shirasaki, Takayoshi, Le Voyer, Tom, Guérin, Antoine, Bastard, Paul, Moncada-Vélez, Marcela, Han, Ji Eun, Khan, Taushif, Rapaport, Franck, Hong, Seon-Hui, Cheung, Andrew, Haake, Kathrin, Mindt, Barbara C., Pérez, Laura, Philippot, Quentin, Lee, Danyel, Zhang, Peng, Rinchai, Darawan, Al Ali, Fatima, Ahmad Ata, Manar Mahmoud, Rahman, Mahbuba, Peel, Jessica N., Heissel, Søren, Molina, Henrik, Kendir-Demirkol, Yasemin, Bailey, Rasheed, Zhao, Shuxiang, Bohlen, Jonathan, Mancini, Mathieu, Seeleuthner, Yoann, Roelens, Marie, Lorenzo, Lazaro, Soudée, Camille, Paz, María Elvira Josefina, González, María Laura, Jeljeli, Mohamed, Soulier, Jean, Romana, Serge, L’Honneur, Anne-Sophie, Materna, Marie, Martínez-Barricarte, Rubén, Pochon, Mathieu, Oleaga-Quintas, Carmen, Michev, Alexandre, Migaud, Mélanie, Lévy, Romain, Alyanakian, Marie-Alexandra, Rozenberg, Flore, Croft, Carys A., Vogt, Guillaume, Emile, Jean-François, Kremer, Laurent, Ma, Cindy S., Fritz, Jörg H., Lemon, Stanley M., Spaan, András N., Manel, Nicolas, Abel, Laurent, MacDonald, Margaret R., Boisson-Dupuis, Stéphanie, Marr, Nico, Tangye, Stuart G., Di Santo, James P., Zhang, Qian, Zhang, Shen-Ying, Rice, Charles M., Béziat, Vivien, Lachmann, Nico, Langlais, David, Casanova, Jean-Laurent, Gros, Philippe, and Bustamante, Jacinta

Published
2023
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5. Transcriptome immune-regulatory differences between leprosy patients and type 1 reaction patients, before onset of symptoms.

Author

Correa-Macedo, Wilian, Dallmann-Sauer, Monica, Orlova, Marianna, Manry, Jeremy, Fava, Vinicius M., Huong, Nguyen Thu, Ba, Nguyen Ngoc, Van Thuc, Nguyen, Thai, Vu Hong, and Schurr, Erwin

Subjects
MYCOBACTERIUM leprae, PERIPHERAL neuropathy, HANSEN'S disease, PYROPTOSIS, INTRACELLULAR pathogens
Abstract

Leprosy is a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. A major public health and clinical problem are leprosy reactions, which are inflammatory episodes that often contribute to nerve damage and disability. Type I reversal reactions (T1R) can occur after microbiological cure of leprosy and affect up to 50% of leprosy patients. Early intervention to prevent T1R and, hence, nerve damage, is a major focus of current leprosy control efforts. In a prospective study, we enrolled and collected samples from 32 leprosy patients before the onset of T1R. Whole blood aliquots were challenged with M. leprae sonicate or media and total RNA was extracted. After a three-year follow-up, the transcriptomic response was compared between cells from 22 patients who remained T1R-free and 10 patients who developed T1R during that period. Our analysis focused on differential transcript (i.e. isoform) expression and usage. Results showed that, at baseline, cells from T1R-destined and T1R-free subjects had no main difference in their transcripts expression and usage. However, the cells of T1R patients displayed a transcriptomic immune response to M. leprae antigens that was significantly different from the one of cells from leprosy patients who remained T1R-free. Transcripts with significantly higher upregulation in the T1R-destined group, compared to the cells from T1R-free patients, were enriched for pathways and GO terms involved in response to intracellular pathogens, apoptosis regulation and inflammatory processes. Similarly, transcript usage analysis pinpointed different transcript proportions in response to the in-vitro challenge of cells from T1R-destined patients. Hence, transcript usage in concert with transcript expression suggested a dysregulated inflammatory response including increased apoptosis regulation in the peripheral blood cells of T1R-destined patients before the onset of T1R symptoms. Combined, these results provided detailed insight into the pathogenesis of T1R. Author summary: The prevention and clinical management of type 1 reactions (T1R) remain an important unmet need to reduce nerve damage in leprosy patients. It is not known why 30–50% of leprosy patients will develop T1R. This knowledge gap underlies the need for a better mechanistic understanding of T1R that could lead to biomarker candidates to identify leprosy patients who are at high risk of developing T1R. Here, we used a prospective design in which leprosy patients were enrolled before the onset of T1R.Whole blood samples were obtained at enrollment, aliquots were left unstimulated or were stimulated M. leprae antigens and total RNA was extracted. Patients were followed for three years at which time 10 out of 32 participants had developed T1R. Subsequent transcript expression and usage analyses revealed that groups differed little in their isoform landscape at baseline. Following stimulation, transcriptomic response differences became pronounced. Transcripts with higher response in T1R group preferentially involved genes of intracellular defense and inflammatory pathways. Among these transcripts, non-coding ones had higher frequency in T1R. Our study provided new insights into the T1R pathogenesis by suggesting a role for non-coding transcripts into the immune dysregulations of T1R and providing additional candidate genes and their isoforms to be further investigated. [ABSTRACT FROM AUTHOR]

Published
2024
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7. A novel pediatric polycystic lung disease caused by CCR2 deficiency

Author

Neehus, Anna-Lena, primary, Landekic, Marija, additional, Rinchai, Darawan, additional, Panikulam, Patricia, additional, Philippot, Quentin, additional, Le Voyer, Tom, additional, Ogishi, Masato, additional, Rosain, Jérémie, additional, Momenilandi, Mana, additional, Andrés Arango Franco, Carlos, additional, Martin-Fernandez, Marta, additional, Khan, Taushif, additional, Bohlen, Jonathan, additional, Manry, Jeremy, additional, Eun Han, Ji, additional, Deslys, Alexandre, additional, Gajardo-Carrasco, Tania, additional, Soudée, Camille, additional, Migaud, Melanie, additional, Seeleuthner, Yoann, additional, Nikolouli, Eirini, additional, Seyedpour, Simin, additional, Begueret, Hugues, additional, Brouzes, Chantal, additional, Vargas, Pablo, additional, Lachmann, Nico, additional, Boire, Raphael, additional, Marr, Nico, additional, Bugonovic, Dusan, additional, Modaresi, Mohammadreza, additional, Nogee, Larry, additional, Craven, Daniel, additional, Mohamadzadeh, Iraj, additional, Rezai, Nima, additional, Shahrooei, Mohammad, additional, Boisson-Dupuis, Stephanie, additional, Sepulveda, Fernando, additional, Béziat, Vivien, additional, Aladjidi, Nathalie, additional, Abel, Laurent, additional, Gros, Philippe, additional, Malo, Danielle, additional, Young, Lisa, additional, Deterding, Robin, additional, Deutsch, Gail, additional, Carey, Brenna, additional, Trapnell, Bruce, additional, Casanova, Jean-Laurent, additional, and Bustamante, Jacinta, additional

Published
2023
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11. Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency

Author

Bastard, Paul, Manry, Jeremy, Chen, Jie, Rosain, Jeremie, Seeleuthner, Yoann, AbuZaitun, Omar, Lorenzo, Lazaro, Khan, Taushif, Hasek, Mary, Hernandez, Nicholas, Bigio, Benedetta, Zhang, Peng, Levy, Romain, Shrot, Shai, Reino, Eduardo J. Garcia, Lee, Yoon-Seung, Boucherit, Soraya, Aubart, Melodie, Gijsbers, Rik, Beziat, Vivien, Li, Zhi, Pellegrini, Sandra, Rozenberg, Flore, Marr, Nico, Meyts, Isabelle, Boisson, Bertrand, Cobat, Aurelie, Bustamante, Jacinta, Zhang, Qian, Jouangy, Emmanuelle, Abel, Laurent, Somech, Raz, Casanova, Jean-Laurent, and Zhang, Shen-Ying

Subjects
Interferon -- Health aspects, Herpes simplex -- Genetic aspects -- Complications and side effects -- Care and treatment, Encephalitis -- Genetic aspects -- Development and progression -- Care and treatment, Health care industry
Abstract

Inborn errors of TLR3-dependent IFN-[alpha]/[beta]- and IFN-[lambda]-mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions of IFN-[alpha]/[beta] and IFN-[lambda] are unknown. We report a child homozygous for a genomic deletion of the entire coding sequence and part of the 3'-UTR of the last exon of IFNAR1, who died of HSE at the age of 2 years. An older cousin died following vaccination against measles, mumps, and rubella at 12 months of age, and another 17-year-old cousin homozygous for the same variant has had other, less severe, viral illnesses. The encoded IFNAR1 protein is expressed on the cell surface but is truncated and cannot interact with the tyrosine kinase TYK2. The patient's fibroblasts and EBV-B cells did not respond to IFN-[alpha]2b or IFN-[beta], in terms of STAT1, STAT2, and STAT3 phosphorylation or the genome-wide induction of IFN-stimulated genes. The patient's fibroblasts were susceptible to viruses, including HSV-1, even in the presence of exogenous IFN-[alpha]2b or IFN-[beta]. HSE is therefore a consequence of inherited complete IFNAR1 deficiency. This viral disease occurred in natural conditions, unlike those previously reported in other patients with IFNAR1 or IFNAR2 deficiency. This experiment of nature indicates that IFN-[alpha]/[beta] are essential for anti-HSV-1 immunity in the CNS., Introduction Herpes simplex virus 1 (HSV-1) is an [alpha]-herpesvirus that infects about 75% of the general population by the age of 18 years (1, 2). Following primary infection, it typically [...]

Published
2021
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12. Additional file 1 of Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Author

Matuozzo, Daniela, Talouarn, Estelle, Marchal, Astrid, Zhang, Peng, Manry, Jeremy, Seeleuthner, Yoann, Zhang, Yu, Bolze, Alexandre, Chaldebas, Matthieu, Milisavljevic, Baptiste, Gervais, Adrian, Bastard, Paul, Asano, Takaki, Bizien, Lucy, Barzaghi, Federica, Abolhassani, Hassan, Abou Tayoun, Ahmad, Aiuti, Alessandro, Alavi Darazam, Ilad, Allende, Luis M., Alonso-Arias, Rebeca, Arias, Andrés Augusto, Aytekin, Gokhan, Bergman, Peter, Bondesan, Simone, Bryceson, Yenan T., Bustos, Ingrid G., Cabrera-Marante, Oscar, Carcel, Sheila, Carrera, Paola, Casari, Giorgio, Chaïbi, Khalil, Colobran, Roger, Condino-Neto, Antonio, Covill, Laura E., Delmonte, Ottavia M., El Zein, Loubna, Flores, Carlos, Gregersen, Peter K., Gut, Marta, Haerynck, Filomeen, Halwani, Rabih, Hancerli, Selda, Hammarström, Lennart, Hatipoğlu, Nevin, Karbuz, Adem, Keles, Sevgi, Kyheng, Christèle, Leon-Lopez, Rafael, Franco, Jose Luis, Mansouri, Davood, Martinez-Picado, Javier, Metin Akcan, Ozge, Migeotte, Isabelle, Morange, Pierre-Emmanuel, Morelle, Guillaume, Martin-Nalda, Andrea, Novelli, Giuseppe, Novelli, Antonio, Ozcelik, Tayfun, Palabiyik, Figen, Pan-Hammarström, Qiang, de Diego, Rebeca Pérez, Planas-Serra, Laura, Pleguezuelo, Daniel E., Prando, Carolina, Pujol, Aurora, Reyes, Luis Felipe, Rivière, Jacques G., Rodriguez-Gallego, Carlos, Rojas, Julian, Rovere-Querini, Patrizia, Schlüter, Agatha, Shahrooei, Mohammad, Sobh, Ali, Soler-Palacin, Pere, Tandjaoui-Lambiotte, Yacine, Tipu, Imran, Tresoldi, Cristina, Troya, Jesus, van de Beek, Diederik, Zatz, Mayana, Zawadzki, Pawel, Al-Muhsen, Saleh Zaid, Alosaimi, Mohammed Faraj, Alsohime, Fahad M., Baris-Feldman, Hagit, Butte, Manish J., Constantinescu, Stefan N., Cooper, Megan A., Dalgard, Clifton L., Fellay, Jacques, Heath, James R., Lau, Yu-Lung, Lifton, Richard P., Maniatis, Tom, Mogensen, Trine H., von Bernuth, Horst, Lermine, Alban, Vidaud, Michel, Boland, Anne, Deleuze, Jean-François, Nussbaum, Robert, Kahn-Kirby, Amanda, Mentre, France, Tubiana, Sarah, Gorochov, Guy, Tubach, Florence, Hausfater, Pierre, Meyts, Isabelle, Zhang, Shen-Ying, Puel, Anne, Notarangelo, Luigi D., Boisson-Dupuis, Stephanie, Su, Helen C., Boisson, Bertrand, Jouanguy, Emmanuelle, Casanova, Jean-Laurent, Zhang, Qian, Abel, Laurent, and Cobat, Aurélie

Abstract

Additional file 1: Supplementary Methods. Fig S1. Luciferase assay on HEK293T cells transfected with the pGL4.32 luciferase reporter construct and an expression vector for Renilla luciferase together with no vector (mock), EV, WT, or 4 TLR7 variants found in our cohort. After 24 h, transfected cells were left untreated or were treated by incubation with 1 μg/mL R848 for 24 h. These data were established from two independent experiments. The y-axis represents NF-κB transcriptional activity as a percentage of the WT. The x-axis indicates the alleles used for transfection. Fig S2. Age distribution as boxplot and violin plot of the critical COVID-19 cases according to the carrier status of pLOF/bLOF at 15 type I IFN-related loci. Mean age of the patients for each category is shown in red. T-test was used to compare the means, showing a significant difference between non-carriers and carriers of heterozygous or homozygous/hemizygous variants (P = 2.2 × 10−6) and between heterozygous carriers and homozygous/hemizygous carriers (P = 0.008). Fig S3. Empirical power of our sample to detect an association at the 2.5 × 10−6 exome-wide significance threshold for various relative risks and proportion of carriers of at least one disease causing variant in the general population (PD), as estimated by simulation study (N = 1000 replicates).

Published
2023
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13. Autoantibodies against type I IFNs in patients with critical influenza pneumonia

Author

Zhang, Qian, Pizzorno, Andrés, Miorin, Lisa, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Manry, Jeremy, Rosain, Jérémie, Philippot, Quentin, Goavec, Kelian, Wroblewski, Isabelle, Husebye, Eystein, Fellay, Jacques, Pothier, Pierre, Morand, Patrice, Navarrete, Nicolás, Franco, José Luis, Uddin, Mohammed J., Carratalà, Jordi, Merino Díaz, Laura, Palomo, Virginia, Seppänen, Mikko R.J., Särekannu, Karita, Aiuti, Alessandro, Retamar Gentil, Pilar, Debette, Stéphanie, Belot, Alexandre, Abel, Laurent, Soler Palacín, Pere, Abad Arranz, Maria, Aguilar Guisado, Manuela, Meyts, Isabelle, Casanova, Jean-Laurent, Gonzalez Granado, Luis L., Butte, Manish J., Itan, Yuval, Escoresca Ortega, Ana, Morio, Tomohiro, Padey, Blandine, Niubó, Jordi, Gallardo Ríos, Rafaela, Lau, Yu-lung, Triantafyllia, Vasiliki, Briones, Marisa, Saker, Kahina, Richard, Pascale, Drolet, Beth A., Espinosa Padilla, Sara, Wauters, Joost, Peigue Lafeuille, Helene, Valiente, Adoración, El Baghdadi, Jamila, Tiberghien, Pierre, Balsera-manzanero, María, Zins, Marie, Hammarström, Lennart, Andreakos, Evangelos, Notarangelo, Luigi D., Prando, Carolina, Condino-neto, Antonio, Dominguez Pinilla, Nerea, Aydillo, Teresa, Okamoto, Keisuke, Soumaré, Aïcha, Karamitros, Timokratis, Medina, Rafael A., Kisand, Kai, Ramírez Duque, Nieves, Feys, Simon, Romero Oraa, Laura, Kuo, Chen-yen, Lei, Wei-te, Quintana Murci, Lluis, Milner, Joshua D., Ku, Cheng-lung, Van De Beek, Diederik, Hsieh, Elena W.Y., Tal, Galit, Fournet, Thomas, Cerba Healthcare Group, Patural, Hugues, Novelli, Giuseppe, Lyon Antigrippe Working Group, Arias, Andrés A., Rovina, Nikoletta, Rodríguez-gallego, Carlos, Puel, Anne, Jouanguy, Emmanuelle, Vinh, Donald C., Henny, Joseph, Mogensen, Trine H., Cobat, Aurélie, Casari, Giorgio, Ramaswamy, Sathishkumar, Abelenda Alonso, Gabriela, Morel, Pascal, Trouillet Assant, Sophie, Tzourio, Christophe, Gallian, Pierre, Reipi Inf Working Group, García Sastre, Adolfo, Constantinescu, Stefan N., Hamzeh Cognasse, Hind, Haerynck, Filomeen, Flores, Carlos, Bousfiha, Ahmed A., García Salum, Tamara, Shahrooei, Mohammed, Slaby, Ondrej, Fragkou, Paraskevi C., Argaud, Laurent, Shcherbina, Anna, Al-muhsen, Saleh, Biggs, Catherine M., Bogunovic, Dusan, Planas, Anna M., Heath, James R., Von Bernuth, Horst, Dufouil, Carole, Bolze, Alexandre, Boeuf, Benoit, Rodríguez Gallego, Carlos, Christodoulou, John, Bondarenko, Anastasiia, Martin, Fernando, Koltsida, Ourania, Sediva, Anna, Ruiz Hernandez, José Juan, Bonneaudeau, Brigitte, Cannet, Dorothée, Etablissement Français Du Sang Study Group, Froidure, Antoine, Laurent, Emilie, Galani, Ioanna Evdokia, Gregersen, Peter K., Lemonnier, Sylvie, Spaan, András N., Darmon, Michael, Grimbacher, Bodo, Del Mar Muñoz Garcia, Maria, Zawadzki, Pawel, Henrickson, Sarah E., O'farrelly, Cliona, Rosa Calatrava, Manuel, Lachaize, Morgane, Okada, Satoshi, Vanker, Martti, Bryceson, Yenan, Ling, Yun, Cooper, Megan A., Lucas, Carrie L., Maniatis, Tom, Romero Vázquez, Gloria María, Mansouri, Davood, Castagnoli, Riccardo, Maródi, László, Mironska, Kristina, Rapti, Vasiliki, Baris Feldman, Hagit, Pozzetto, Bruno, Renia, Laurent, Tancevski, Ivan, Imai, Kohsuke, Ozcelik, Tayfun, Pan-hammarström, Qiang, Al-mulla, Fahd, Pape, Jean W., Etzioni, Amos, Souweine, Bertrand, Perez De Diego, Rebeca, Sánchez Cordero, Maria Jose, Solé Violán, Jordi, Perlin, David S., Queromes, Gregory, Anderson, Mark S., Resnick, Igor, Pesole, Graziano, Su, Helen C., Vanderbeke, Lore, Hagin, David, Jeanne, Michel, Desai, Murkesh, Ferres, Marcela, Sánchez Céspedes, Javier, Perroquin, Magali, Ng, Lisa F.P., Abou Tayoun, Ahmad, Le Corre, Nicole, Snow, Andrew L., Temel, Şehime Gülsün, Tsiodras, Sotirios, Coeuret Pellicer, Mireille, Javouhey, Etienne, Turvey, Stuart E., Covid Human Genetic Effort, Rombauts, Alexander, Zatz, Mayana, Uddin, K.m. Furkan, Fievet, Nathalie, Jarvis, Erich D., Rodríguez De Castro, Felipe, Ferreres, José, Flaig, Amandine, Pujol, Aurora, Cognasse, Fabrice, Sancho Shimizu, Vanessa, Nadif, Rachel, Hanna, Suhair, Constances Cohort, Goldberg, Marcel, Brodin, Petter, Le Got, Stéphane, Ozguler, Anna, Quenot, Jean Pierre, Novelli, Antonio, Cordero, Elisa, Colomb, Benoit, Cupic, Anastasija, Mehlal Sedkaoui, Souad, Sallette, Jérôme, Hernu, Romain, Bustamante, Carlos D., Lina, Bruno, Halwani, Rabih, Casalegno, Jean Sebastien, Schwebel, Carole, Salamanca Rivera, Celia, 3C-Dijon Study, Tangye, Stuart G., Dalgard, Clifton L., Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), European Commission, Square Foundation, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université Paris Cité, Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), Center of Excellence for Influenza Research and Response (US) CEIRR, Agencia Nacional de Investigación y Desarrollo (Chile), Centre National de la Recherche Scientifique (France), Ministère des Solidarités et de la Santé (France), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Sociedad Española de Neumología y Cirugía Torácica, Cabildo de Tenerife, Hellenic Foundation for Research and Innovation, Fondation pour la Recherche Médicale, Fondation Bettencourt Schueller, Ministerio de Ciencia, Innovación y Universidades (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Junta de Andalucía, Research Foundation - Flanders, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-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), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 01057100, HORIZON-HLTH-2021-DISEASE-04, MESRI-COVID-19, ANR-10-LABX-62-IBEID, P18-RT-3320, CGIEU0000219140, RTC-2017-6471-1, REIPI RD16/0016/0009, National Institutes of Health, NIH: R01AI088364, R01AI163029, Howard Hughes Medical Institute, HHMI, National Institute of Allergy and Infectious Diseases, NIAID: 75N93021C00014, U19AI135972, U19AI142733, U19AI168631, Jeffrey Modell Foundation, JMF, Glenn Foundation for Medical Research, GFMR: ANRS-COV05, EA20170638020, EQU201903007798, Pfizer, Albert Ellis Institute, AEI, National Center for Advancing Translational Sciences, NCATS: UL1 TR001866, JPB Foundation, JPBF, Horizon 2020 Framework Programme, H2020: 824110, Fondation du Souffle, FdS, College of Natural Resources and Sciences, Humboldt State University, CNRS, Ministerio de Ciencia, Innovación y Universidades, MCIU, Instituto Tecnológico y de Energías Renovables, ITER, SCOR Corporate Foundation for Science, Agence Nationale de la Recherche, ANR: ANR-10-IAHU-01, Institut National de la Santé et de la Recherche Médicale, Inserm, Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT: 1161971, 1212023, Association Nationale de la Recherche et de la Technologie, ANRT, Fonds Wetenschappelijk Onderzoek, FWO: G0B5120N, G0C8517N, G0E8420N, KU Leuven: C16/18/007, Instituto de Salud Carlos III, ISCIII: COV20_01333, COV20_01334, PI12/01565, European Regional Development Fund, ERDF: CB21/13/00006, University of the East, UE, Hellenic Foundation for Research and Innovation, ΕΛ.ΙΔ.Ε.Κ, Université de Paris, SINOVAC outside the submitted work. P. Retamar-Gentil reported personal fees from Merck outside the submitted work. I. Meyts reported grants from CSL-Behring outside the submitted work. E. Andreakos reported grants from Janssen Pharmaceuticals during the conduct of the study. J. Wauters reported grants and personal fees from Pfizer and Gilead outside the submitted work. L. Vanderbeke reported grants from Research Foundation Flanders and non-financial support from Pfizer outside the submitted work. S. Feys reported grants from Pfizer outside the submitted work. J. Casalegno reported 'other' from Pfizer and grants from Sanofi outside the submitted work. M. Rosa-Calatrava reported a patent to WO2016/146836 licensed (Signia Therapeutics), a patent to WO2017/174593 licensed (Signia Therapeutics), and a patent to WO2019/224489 licensed (Signia Therapeutics), and is the co-founder of Signia Therapeutics SAS. S. Trouillet-Assant reported non-financial support from BioMérieux outside the submitted work. A. Garcia-Sastre reported 'other' from Vivaldi Biosciences, Pagoda, Contrafect, Vaxalto, Accurius, Curelab oncology, and Curelab veterinary, personal fees from Avimex, 7Hills, Esperovax, Pfizer, Farmak, Applied Biological Laboratories, Paratus, Pharmamar, Pfizer, and Synairgen, grants from Pfizer, Pharmamar, Blade Therapeutics, Avimex, Accurius, Dyna-vax, Kenall Manufacturing, ImmunityBio, Nanocomposix, Merck, Model Medicines, Atea Pharma, Shenwa Biosciences, Johnson & Johnson, 7 Hills, Hexamer, N-fold LLC, and Applied Biological Laboratories outside the submitted work, in addition, A. Garcia-Sastre had a patent for influenza virus vaccines and uses thereof issued, and invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. J. Casanova reported a patent to PCT/US2021/ 042741 pending. No other disclosures were reported., We thank Dr. Cato Jacobs for her contribution to the sampling of UZLeuven patients in Belgium. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, 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), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Sci-ence, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmis-sion, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cab-ildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Eu-rope', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University. Author contributions: Q. Zhang, A. Pizzorno, L. Miorin, P., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, 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), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and, Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Europe', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University., ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), 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-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), and ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021)

Subjects
INTERFERON, Cerba HealthCare Group, Immunology, SEVERE COVID-19, Pneumònia, Autoanticossos, DETERMINANTS, IMMUNITY, Grip, NEUTRALIZING ANTIBODIES, 3C-Dijon Study, INFECTION, Influenza, Human, Medicine and Health Sciences, Immunology and Allergy, Humans, COVID Human Genetic Effort, MYASTHENIA-GRAVIS PATIENTS, Autoantibodies, REIPI INF Working Group, Etablissement Français du Sang Study Group, Yellow Fever Vaccine, COVID-19, Pneumonia, ALLELES, Lyon Antigrippe Working Group, Influenza, ALPHA, Settore MED/03, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, BURDEN, Constances Cohort
Abstract

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH; R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, 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), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y Desarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19”). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009); cofinanced by European Regional Development Fund “A way to achieve Europe”; Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University.

Published
2022
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15. Human genetic and immunological determinants of critical COVID-19 pneumonia

Author

Zhang, Qian, Bastard, Paul, Karbuz, Adem, Gervais, Adrian, Tayoun, Ahmad Abou, Aiuti, Alessandro, Belot, Alexandre, Bolze, Alexandre, Gaudet, Alexandre, Bondarenko, Anastasiia, Liu, Zhiyong, Spaan, András, Guennoun, Andrea, Arias, Andres Augusto, Planas, Anna, Sediva, Anna, Shcherbina, Anna, Neehus, Anna-Lena, Puel, Anne, Froidure, Antoine, Novelli, Antonio, Parlakay, Aslınur Özkaya, Pujol, Aurora, Yahşi, Aysun, Gülhan, Belgin, Bigio, Benedetta, Boisson, Bertrand, Drolet, Beth, Franco, Carlos Andres Arango, Flores, Carlos, Rodríguez-Gallego, Carlos, Prando, Carolina, Biggs, Catherine, Luyt, Charles-Edouard, Dalgard, Clifton, O’Farrelly, Cliona, Matuozzo, Daniela, Dalmau, David, Perlin, David, Mansouri, Davood, van de Beek, Diederik, Vinh, Donald, Dominguez-Garrido, Elena, Hsieh, Elena, Erdeniz, Emine Hafize, Jouanguy, Emmanuelle, Şevketoglu, Esra, Talouarn, Estelle, Quiros-Roldan, Eugenia, Andreakos, Evangelos, Husebye, Eystein, Alsohime, Fahad, Haerynck, Filomeen, Casari, Giorgio, Novelli, Giuseppe, Aytekin, Gökhan, Morelle, Guillaume, Alkan, Gulsum, Bayhan, Gulsum Iclal, Feldman, Hagit Baris, Su, Helen, von Bernuth, Horst, Resnick, Igor, Bustos, Ingrid, Meyts, Isabelle, Migeotte, Isabelle, Tancevski, Ivan, Bustamante, Jacinta, Fellay, Jacques, El Baghdadi, Jamila, Martinez-Picado, Javier, Casanova, Jean-Laurent, Rosain, Jeremie, Manry, Jeremy, Chen, Jie, Christodoulou, John, Bohlen, Jonathan, Franco, José Luis, Li, Juan, Anaya, Juan Manuel, Rojas, Julian, Ye, Junqiang, Uddin, K., Yasar, Kadriye Kart, Kisand, Kai, Okamoto, Keisuke, Chaïbi, Khalil, Mironska, Kristina, Maródi, László, Abel, Laurent, Renia, Laurent, Lorenzo, Lazaro, Hammarström, Lennart, Ng, Lisa, Quintana-Murci, Lluis, Erazo, Lucia Victoria, Notarangelo, Luigi, Reyes, Luis Felipe, Allende, Luis, Imberti, Luisa, Renkilaraj, Majistor Raj Luxman Maglorius, Moncada-Velez, Marcela, Materna, Marie, Anderson, Mark, Gut, Marta, Chbihi, Marwa, Ogishi, Masato, Emiroglu, Melike, Seppänen, Mikko, Uddin, Mohammed, Shahrooei, Mohammed, Alexander, Natalie, Hatipoglu, Nevin, Marr, Nico, Akçay, Nihal, Boyarchuk, Oksana, Slaby, Ondrej, Akcan, Ozge Metin, Zhang, Peng, Soler-Palacín, Pere, Gregersen, Peter, Brodin, Petter, Garçon, Pierre, Morange, Pierre-Emmanuel, Pan-Hammarström, Qiang, Zhou, Qinhua, Philippot, Quentin, Halwani, Rabih, de Diego, Rebeca Perez, Levy, Romain, Yang, Rui, Öz, Şadiye Kübra Tüter, Muhsen, Saleh Al, Kanık-Yüksek, Saliha, Espinosa-Padilla, Sara, Ramaswamy, Sathishkumar, Okada, Satoshi, Bozdemir, Sefika Elmas, Aytekin, Selma Erol, Karabela, Şemsi Nur, Keles, Sevgi, Senoglu, Sevtap, Zhang, Shen-Ying, Duvlis, Sotirija, Constantinescu, Stefan, Boisson-Dupuis, Stephanie, Turvey, Stuart, Tangye, Stuart, Asano, Takaki, Ozcelik, Tayfun, Le Voyer, Tom, Maniatis, Tom, Morio, Tomohiro, Mogensen, Trine, Sancho-Shimizu, Vanessa, Beziat, Vivien, Solanich, Xavier, Bryceson, Yenan, Lau, Yu-Lung, Itan, Yuval, Cobat, Aurélie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Effort, COVID Human Genetic, Özçelik, Tayfun, Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Yale University, Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, European Commission, Square Foundation, Ministère de l’Enseignement supérieur et de la Recherche (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondation Bettencourt Schueller, Regione Lazio, National Institute of Allergy and Infectious Diseases (US), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-20-COV6-0001,CRISPR-TARGET-CoV,Cribles CRISPR à l'échelle du génome pour identifier de nouvelles cibles thérapeutiques et inhiber la réplication du SARS-CoV-2(2020), Zhang, Q., Bastard, P., Karbuz, A., Gervais, A., Tayoun, A. A., Aiuti, A., Belot, A., Bolze, A., Gaudet, A., Bondarenko, A., Spaan, A. N., Guennoun, A., Arias, A. A., Planas, A. M., Sediva, A., Shcherbina, A., Neehus, A. -L., Puel, A., Froidure, A., Novelli, A., Parlakay, A. O., Pujol, A., Yahsi, A., Gulhan, B., Bigio, B., Boisson, B., Drolet, B. A., Franco, C. A. A., Flores, C., Rodriguez-Gallego, C., Prando, C., Biggs, C. M., Luyt, C. -E., Dalgard, C. L., O'Farrelly, C., Matuozzo, D., Dalmau, D., Perlin, D. S., Mansouri, D., van de Beek, D., Vinh, D. C., Dominguez-Garrido, E., Hsieh, E. W. Y., Erdeniz, E. H., Jouanguy, E., Sevketoglu, E., Talouarn, E., Quiros-Roldan, E., Andreakos, E., Husebye, E., Alsohime, F., Haerynck, F., Casari, G., Novelli, G., Aytekin, G., Morelle, G., Alkan, G., Bayhan, G. I., Feldman, H. B., Su, H. C., von Bernuth, H., Resnick, I., Bustos, I., Meyts, I., Migeotte, I., Tancevski, I., Bustamantem, J., Fellay, J., El Baghdadi, J., Martinez-Picado, J., Casanova, J. -L., Rosain, J., Manry, J., Chen, J., Christodoulou, J., Bohlen, J., Franco, J. L., Li, J., Anaya, J. M., Rojas, J., Ye, J., Uddin, K. M. F., Yasar, K. K., Kisand, K., Okamoto, K., Chaibi, K., Mironska, K., Marodi, L., Abel, L., Renia, L., Lorenzo, L., Hammarstrom, L., Ng, L. F. P., Quintana-Murci, L., Erazo, L. V., Notarangelo, L. D., Reyes, L. F., Allende, L. M., Imberti, L., Renkilaraj, M. R. L. M., Moncada-Velez, M., Materna, M., Anderson, M. S., Gut, M., Chbihi, M., Ogishi, M., Emiroglu, M., Seppanen, M. R. J., Uddin, M. J., Shahrooei, M., Alexander, N., Hatipoglu, N., Marr, N., Akcay, N., Boyarchuk, O., Slaby, O., Akcan, O. M., Zhang, P., Soler-Palacin, P., Gregersen, P. K., Brodin, P., Garcon, P., Morange, P. -E., Pan-Hammarstrom, Q., Zhou, Q., Philippot, Q., Halwani, R., de Diego, R. P., Levy, R., Yang, R., Oz, S. K. T., Muhsen, S. A., Kanik-Yuksek, S., Espinosa-Padilla, S., Ramaswamy, S., Okada, S., Bozdemir, S. E., Aytekin, S. E., Karabela, S. N., Keles, S., Senoglu, S., Zhang, S. -Y., Duvlis, S., Constantinescu, S. N., Boisson-Dupuis, S., Turvey, S. E., Tangye, S. G., Asano, T., Ozcelik, T., Le Voyer, T., Maniatis, T., Morio, T., Mogensen, T. H., Sancho-Shimizu, V., Beziat, V., Solanich, X., Bryceson, Y., Lau, Y. -L., Itan, Y., and Cobat, A.

Subjects
Multidisciplinary, [SDV]Life Sciences [q-bio], Critical Illness, COVID-19, Dendritic Cells, Article, Toll-Like Receptor 3, Basic medicine, Age Distribution, Toll-Like Receptor 7, Settore MED/03, Interferon Type I, Humans, Autoantibodies, Genome-Wide Association Study, Sex Distribution
Abstract

COVID Human Genetic Effort: Adem Karbuz, Adrian Gervais, Ahmad Abou Tayoun, Alessandro Aiuti, Alexandre Belot, Alexandre Bolze, Alexandre Gaudet, Anastasiia Bondarenko, Zhiyong Liu, András N. Spaan, Andrea Guennoun, Andres Augusto Arias, Anna M. Planas, Anna Sediva, Anna Shcherbina, Anna-Lena Neehus, Anne Puel, Antoine Froidure, Antonio Novelli, Aslınur Özkaya Parlakay, Aurora Pujol, Aysun Yahşi, Belgin Gülhan, Benedetta Bigio, Bertrand Boisson, Beth A. Drolet, Carlos Andres Arango Franco, Carlos Flores, Carlos Rodríguez-Gallego, Carolina Prando, Catherine M. Biggs, Charles-Edouard Luyt, Clifton L. Dalgard, Cliona O’Farrelly, Daniela Matuozzo, David Dalmau, David S. Perlin, Davood Mansouri, Diederik van de Beek, Donald C. Vinh, Elena Dominguez-Garrido, Elena W. Y. Hsieh, Emine Hafize Erdeniz, Emmanuelle Jouanguy, Esra Şevketoglu, Estelle Talouarn, Eugenia Quiros-Roldan, Evangelos Andreakos, Eystein Husebye, Fahad Alsohime, Filomeen Haerynck, Giorgio Casari, Giuseppe Novelli, Gökhan Aytekin, Guillaume Morelle, Gulsum Alkan, Gulsum Iclal Bayhan, Hagit Baris Feldman, Helen C. Su, Horst von Bernuth, Igor Resnick, Ingrid Bustos, Isabelle Meyts, Isabelle Migeotte, Ivan Tancevski, Jacinta Bustamante, Jacques Fellay, Jamila El Baghdadi, Javier Martinez-Picado, Jean-Laurent Casanova, Jeremie Rosain, Jeremy Manry, Jie Chen, John Christodoulou, Jonathan Bohlen, José Luis Franco, Juan Li, Juan Manuel Anaya, Julian Rojas, Junqiang Ye, K. M. Furkan Uddin, Kadriye Kart Yasar, Kai Kisand, Keisuke Okamoto, Khalil Chaïbi, Kristina Mironska, László Maródi, Laurent Abel, Laurent Renia, Lazaro Lorenzo, Lennart Hammarström, Lisa F. P. Ng, Lluis Quintana-Murci, Lucia Victoria Erazo, Luigi D. Notarangelo, Luis Felipe Reyes, Luis M. Allende, Luisa Imberti, Majistor Raj Luxman Maglorius Renkilaraj, Marcela Moncada-Velez, Marie Materna, Mark S. Anderson, Marta Gut, Marwa Chbihi, Masato Ogishi, Melike Emiroglu, Mikko R. J. Seppänen, Mohammed J. Uddin, Mohammed Shahrooei, Natalie Alexander, Nevin Hatipoglu, Nico Marr, Nihal Akçay, Oksana Boyarchuk, Ondrej Slaby, Ozge Metin Akcan, Peng Zhang, Pere Soler-Palacín, Peter K. Gregersen, Petter Brodin, Pierre Garçon, Pierre-Emmanuel Morange, Qiang Pan-Hammarström, Qinhua Zhou, Quentin Philippot, Rabih Halwani, Rebeca Perez de Diego, Romain Levy, Rui Yang, Şadiye Kübra Tüter Öz, Saleh Al Muhsen, Saliha Kanık-Yüksek, Sara Espinosa-Padilla, Sathishkumar Ramaswamy, Satoshi Okada, Sefika Elmas Bozdemir, Selma Erol Aytekin, Şemsi Nur Karabela, Sevgi Keles, Sevtap Senoglu, Shen-Ying Zhang, Sotirija Duvlis, Stefan N. Constantinescu, Stephanie Boisson-Dupuis, Stuart E. Turvey, Stuart G. Tangye, Takaki Asano, Tayfun Ozcelik, Tom Le Voyer, Tom Maniatis, Tomohiro Morio, Trine H. Mogensen, Vanessa Sancho-Shimizu, Vivien Beziat, Xavier Solanich, Yenan Bryceson, Yu-Lung Lau & Yuval Itan, SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1–5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15–20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, 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), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR grant GENVIR (ANR-20-CE93-003), ANR AABIFNCOV (ANR-20-CO11-0001) and ANR MIS-C (ANR 21-COVR-0039, GenMIS-C) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir—Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. P.B. was supported by the FRM (EA20170638020) and the MD-PhD programme of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). G.N. is supported by Regione Lazio (Research Group Projects 2020) no. A0375-2020-36663, GecoBiomark. H.C.S. and L.D.N. are supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Published
2022
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17. The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies

Author

Manry, Jeremy, primary, Bastard, Paul, additional, Gervais, Adrian, additional, Voyer, Tom Le, additional, Rosain, Jérémie, additional, Philippot, Quentin, additional, Michailidis, Eleftherios, additional, Hoffmann, Hans-Heinrich, additional, Eto, Shohei, additional, Garcia-Prat, Marina, additional, Bizien, Lucy, additional, Parra-Martínez, Alba, additional, Yang, Rui, additional, Haljasmägi, Liis, additional, Migaud, Mélanie, additional, Särekannu, Karita, additional, Maslovskaja, Julia, additional, de Prost, Nicolas, additional, Tandjaoui-Lambiotte, Yacine, additional, Luyt, Charles-Edouard, additional, Amador-Borrero, Blanca, additional, Gaudet, Alexandre, additional, Poissy, Julien, additional, Morel, Pascal, additional, Richard, Pascale, additional, Cognasse, Fabrice, additional, Troya, Jesus, additional, Trouillet-Assant, Sophie, additional, Belot, Alexandre, additional, Saker, Kahina, additional, Garçon, Pierre, additional, Rivière, Jacques G., additional, Lagier, Jean-Christophe, additional, Gentile, Stéphanie, additional, Rosen, Lindsey, additional, Shaw, Elana, additional, Morio, Tomohiro, additional, Tanaka, Junko, additional, Dalmau, David, additional, Tharaux, Pierre-Louis, additional, Sene, Damien, additional, Stepanian, Alain, additional, Mégarbane, Bruno, additional, Triantafyllia, Vasiliki, additional, Fekkar, Arnaud, additional, Heath, James, additional, Franco, Jose, additional, Anaya, Juan-Manuel, additional, Solé-Violán, Jordi, additional, Imberti, Luisa, additional, Biondi, Andrea, additional, Bonfanti, Paolo, additional, Castagnoli, Riccardo, additional, Delmonte, Ottavia, additional, Zhang, Yu, additional, Snow, Andrew, additional, Holland, Steve, additional, Biggs, Catherine, additional, Moncada-Vélez, Marcela, additional, Arias, Andrés, additional, Lorenzo, Lazaro, additional, Boucherit, Soraya, additional, Anglicheau, Dany, additional, Planas, Anna, additional, Haerynck, Filomeen, additional, Duvlis, Sotirija, additional, Nussbaum, Robert, additional, Ozcelik, Tayfun, additional, Keles, Sevgi, additional, Bousfiha, Aziz, additional, Bakkouri, Jalila El, additional, Ramirez-Santana, Carolina, additional, Paul, Stéphane, additional, Pan-Hammarstrom, Qiang, additional, Hammarstrom, Lennart, additional, Dupont, Annabelle, additional, Kurolap, Alina, additional, Metz, Christine, additional, Aiuti, Alessandro, additional, Casari, Giorgio, additional, Lampasona, Vito, additional, Ciceri, Fabio, additional, Barreiros, Lucila, additional, Dominguez-Garrido, Elena, additional, Vidigal, Mateus, additional, Zatz, Mayana, additional, de Beek, Diederik van, additional, Sahanic, Sabina, additional, Tancevski, Ivan, additional, Stepanovskyy, Yurii, additional, Boyarchuk, Oksana, additional, Nukui, Yoko, additional, Tsumura, Miyuki, additional, Vidaur, Loreto, additional, Tangye, Stuart, additional, Burrel, Sonia, additional, Duffy, Darragh, additional, Quintana-Murci, Lluis, additional, Klocperk, Adam, additional, Kann, Nelli, additional, Shcherbina, Anna, additional, Lau, Yu-Lung, additional, Leung, Daniel, additional, Coulongeat, Matthieu, additional, Marlet, Julien, additional, Koning, Rutger, additional, Reyes, Luis, additional, Chauvineau-Grenier, Angélique, additional, Venet, Fabienne, additional, monneret, guillaume, additional, Nussenzweig, Michel, additional, Arrestier, Romain, additional, Boudhabhay, Idris, additional, Baris-Feldman, Hagit, additional, Hagin, David, additional, Wauters, Joost, additional, Meyts, Isabelle, additional, Dyer, Adam, additional, Kennelly, Sean, additional, Bourke, Nollaig, additional, Halwani, Rabih, additional, Sharif-Askari, Fatemeh, additional, Dorgham, Karim, additional, Sallette, Jérôme, additional, Mehlal-Sedkaoui, Souad, additional, AlKhater, Suzan, additional, Rigo-Bonnin, Raúl, additional, Morandeira, Francisco, additional, Roussel, Lucie, additional, Vinh, Donald, additional, Erikstrup, Christian, additional, Condino-Neto, Antonio, additional, Prando, Carolina, additional, Bondarenko, Anastasiia, additional, Spaan, András, additional, Gilardin, Laurent, additional, Fellay, Jacques, additional, Lyonnet, Stanislas, additional, Bilguvar, Kaya, additional, Lifton, Richard, additional, Mane, Shrikant, additional, Anderson, Mark, additional, Boisson, Bertrand, additional, Béziat, Vivien, additional, Zhang, Shen-Ying, additional, Andreakos, Evangelos, additional, Hermine, Olivier, additional, Pujol, Aurora, additional, Peterson, Pärt, additional, Mogensen, Trine Hyrup, additional, Rowen, Lee, additional, Mond, James, additional, Debette, Stéphanie, additional, deLamballerie, Xavier, additional, Burdet, Charles, additional, Bouadma, Lila, additional, Zins, Marie, additional, Soler-Palacin, Pere, additional, Colobran, Roger, additional, Gorochov, Guy, additional, Solanich, Xavier, additional, Susen, Sophie, additional, Martinez-Picado, Javier, additional, Raoult, Didier, additional, Vasse, Marc, additional, Gregersen, Peter, additional, Rodríguez-Gallego, Carlos, additional, Piemonti, Lorenzo, additional, Notarangelo, Luigi, additional, Su, Helen, additional, Kisand, Kai, additional, Okada, Satoshi, additional, Puel, Anne, additional, Jouanguy, Emmanuelle, additional, Rice, Charles, additional, Tiberghien, Pierre, additional, Zhang, Qian, additional, Casanova, Jean-Laurent, additional, Abel, Laurent, additional, and Cobat, Aurélie, additional

Published
2022
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18. Inborn errors of TLR3- or MDA5-dependent type I IFN immunity in children with enterovirus rhombencephalitis

Author

Chen, Jie, primary, Jing, Huie, additional, Martin-Nalda, Andrea, additional, Bastard, Paul, additional, Rivière, Jacques G., additional, Liu, Zhiyong, additional, Colobran, Roger, additional, Lee, Danyel, additional, Tung, Wesley, additional, Manry, Jeremy, additional, Hasek, Mary, additional, Boucherit, Soraya, additional, Lorenzo, Lazaro, additional, Rozenberg, Flore, additional, Aubart, Mélodie, additional, Abel, Laurent, additional, Su, Helen C., additional, Soler Palacin, Pere, additional, Casanova, Jean-Laurent, additional, and Zhang, Shen-Ying, additional

Published
2021
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19. Autoantibodies neutralizing type I IFNs are present in similar to 4% of uninfected individuals over 70 years old and account for similar to 20% of COVID-19 deaths

Author

Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jeremie, Philippot, Quentin, Manry, Jeremy, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martinez, Alba, Yang, Rui, Haljasmagi, Liis, Migaud, Melanie, Sarekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesus, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garcon, Pierre, Riviere, Jacques G., Lagier, Jean-Christophe, Gentile, Stephanie, Rosen, Lindsey B., Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R., Franco, Jose Luis, Anaya, Juan-Manuel, Sole-Violan, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M., Zhang, Yu, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Velez, Marcela, Arias, Andres Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M., Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L., Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A., El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stephane, Pan-Hammarstrom, Qiang, Hammarstrom, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N., Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A., Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G., Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli Y., Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angelique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C., Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H., Kennelly, Sean P., Bourke, Nollaig M., Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jerome, Sedkaoui, Souad Mehlal, AlKhater, Suzan, Rigo-Bonnin, Raul, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C., Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, Andras N., Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard P., Mane, Shrikant, Anderson, Mark S., Boisson, Bertrand, Beziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Part, Mogensen, Trine H., Rowen, Lee, Mond, James, Debette, Stephanie, de Lamballerie, Xavier, Duval, Xavier, Mentre, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K., Piemonti, Lorenzo, Rodriguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M., Tiberghien, Pierre, Zhang, Qian, Cobat, Aurelie, Abel, Laurent, Casanova, Jean-Laurent, and Gunst, Jan

Subjects
INTERFERON, alpha, Science & Technology, ANTINUCLEAR, myasthenia-gravis patients, AUTOIMMUNITY, autoimmunity, Immunology, interferon, IMMUNITY, immunity, DISTINCT FUNCTIONS, PATIENT, ALPHA, ANTIBODIES, antibodies, patient, distinct functions, Life Sciences & Biomedicine, MYASTHENIA-GRAVIS PATIENTS, antinuclear
Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases. ispartof: SCIENCE IMMUNOLOGY vol:6 issue:62 ispartof: location:United States status: published

Published
2021

23. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author

Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, I, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, A, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, W, Razooky, B, Hoffmann, H, Michailidis, E, Moens, L, Han, J, Lorenzo, L, Bizien, L, Meade, P, Neehus, A, Ugurbil, A, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schlüter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, M, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, S, Alsohime, F, Al Turki, S, Hasanato, R, van de Beek, D, Biondi, A, Bettini, L, D'Angio, M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, A, Tompkins, M, Alba, C, Vandernoot, I, Goffard, J, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, K, Senoglu, S, Karabela, Ş, Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, A, Dalgard, C, Milner, J, Vinh, D, Mogensen, T, Marr, N, Spaan, A, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, M, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, R, Zhang, S, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, C, Abel, L, Notarangelo, L, Cobat, A, Su, H, Casanova, J, Pesci, A, Zhang, Qian, Bastard, Paul, Liu, Zhiyong, Le Pen, Jérémie, Moncada-Velez, Marcela, Chen, Jie, Ogishi, Masato, Sabli, Ira K D, Hodeib, Stephanie, Korol, Cecilia, Rosain, Jérémie, Bilguvar, Kaya, Ye, Junqiang, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Zhang, Yu, Onodi, Fanny, Korniotis, Sarantis, Karpf, Léa, Philippot, Quentin, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M, Razooky, Brandon S, Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Moens, Leen, Han, Ji Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Corneau, Aurélien, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Seeleuthner, Yoann, Manry, Jeremy, Masson, Cecile, Schmitt, Yohann, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Li, Juan, Fellay, Jacques, Roussel, Lucie, Shahrooei, Mohammad, Alosaimi, Mohammed F, Mansouri, Davood, Al-Saud, Haya, Al-Mulla, Fahd, Almourfi, Feras, Al-Muhsen, Saleh Zaid, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, van de Beek, Diederik, Biondi, Andrea, Bettini, Laura Rachele, D'Angio, Mariella, Bonfanti, Paolo, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Rossi, Camillo, Oler, Andrew J, Tompkins, Miranda F, Alba, Camille, Vandernoot, Isabelle, Goffard, Jean-Christophe, Smits, Guillaume, Migeotte, Isabelle, Haerynck, Filomeen, Soler-Palacin, Pere, Martin-Nalda, Andrea, Colobran, Roger, Morange, Pierre-Emmanuel, Keles, Sevgi, Çölkesen, Fatma, Ozcelik, Tayfun, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Gallego, Carlos Rodríguez, Novelli, Giuseppe, Hraiech, Sami, Tandjaoui-Lambiotte, Yacine, Duval, Xavier, Laouénan, Cédric, Snow, Andrew L, Dalgard, Clifton L, Milner, Joshua, Vinh, Donald C, Mogensen, Trine H, Marr, Nico, Spaan, András N, Boisson, Bertrand, Boisson-Dupuis, Stéphanie, Bustamante, Jacinta, Puel, Anne, Ciancanelli, Michael, Meyts, Isabelle, Maniatis, Tom, Soumelis, Vassili, Amara, Ali, Nussenzweig, Michel, García-Sastre, Adolfo, Krammer, Florian, Pujol, Aurora, Duffy, Darragh, Lifton, Richard, Zhang, Shen-Ying, Gorochov, Guy, Béziat, Vivien, Jouanguy, Emmanuelle, Sancho-Shimizu, Vanessa, Rice, Charles M, Abel, Laurent, Notarangelo, Luigi D, Cobat, Aurélie, Su, Helen C, Casanova, Jean-Laurent, Pesci, Alberto, Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, I, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, A, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, W, Razooky, B, Hoffmann, H, Michailidis, E, Moens, L, Han, J, Lorenzo, L, Bizien, L, Meade, P, Neehus, A, Ugurbil, A, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schlüter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, M, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, S, Alsohime, F, Al Turki, S, Hasanato, R, van de Beek, D, Biondi, A, Bettini, L, D'Angio, M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, A, Tompkins, M, Alba, C, Vandernoot, I, Goffard, J, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, K, Senoglu, S, Karabela, Ş, Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, A, Dalgard, C, Milner, J, Vinh, D, Mogensen, T, Marr, N, Spaan, A, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, M, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, R, Zhang, S, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, C, Abel, L, Notarangelo, L, Cobat, A, Su, H, Casanova, J, Pesci, A, Zhang, Qian, Bastard, Paul, Liu, Zhiyong, Le Pen, Jérémie, Moncada-Velez, Marcela, Chen, Jie, Ogishi, Masato, Sabli, Ira K D, Hodeib, Stephanie, Korol, Cecilia, Rosain, Jérémie, Bilguvar, Kaya, Ye, Junqiang, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Zhang, Yu, Onodi, Fanny, Korniotis, Sarantis, Karpf, Léa, Philippot, Quentin, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M, Razooky, Brandon S, Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Moens, Leen, Han, Ji Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Corneau, Aurélien, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Seeleuthner, Yoann, Manry, Jeremy, Masson, Cecile, Schmitt, Yohann, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Li, Juan, Fellay, Jacques, Roussel, Lucie, Shahrooei, Mohammad, Alosaimi, Mohammed F, Mansouri, Davood, Al-Saud, Haya, Al-Mulla, Fahd, Almourfi, Feras, Al-Muhsen, Saleh Zaid, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, van de Beek, Diederik, Biondi, Andrea, Bettini, Laura Rachele, D'Angio, Mariella, Bonfanti, Paolo, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Rossi, Camillo, Oler, Andrew J, Tompkins, Miranda F, Alba, Camille, Vandernoot, Isabelle, Goffard, Jean-Christophe, Smits, Guillaume, Migeotte, Isabelle, Haerynck, Filomeen, Soler-Palacin, Pere, Martin-Nalda, Andrea, Colobran, Roger, Morange, Pierre-Emmanuel, Keles, Sevgi, Çölkesen, Fatma, Ozcelik, Tayfun, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Gallego, Carlos Rodríguez, Novelli, Giuseppe, Hraiech, Sami, Tandjaoui-Lambiotte, Yacine, Duval, Xavier, Laouénan, Cédric, Snow, Andrew L, Dalgard, Clifton L, Milner, Joshua, Vinh, Donald C, Mogensen, Trine H, Marr, Nico, Spaan, András N, Boisson, Bertrand, Boisson-Dupuis, Stéphanie, Bustamante, Jacinta, Puel, Anne, Ciancanelli, Michael, Meyts, Isabelle, Maniatis, Tom, Soumelis, Vassili, Amara, Ali, Nussenzweig, Michel, García-Sastre, Adolfo, Krammer, Florian, Pujol, Aurora, Duffy, Darragh, Lifton, Richard, Zhang, Shen-Ying, Gorochov, Guy, Béziat, Vivien, Jouanguy, Emmanuelle, Sancho-Shimizu, Vanessa, Rice, Charles M, Abel, Laurent, Notarangelo, Luigi D, Cobat, Aurélie, Su, Helen C, Casanova, Jean-Laurent, and Pesci, Alberto

Abstract

Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Published
2020

24. Genome-wide association study of Buruli ulcer in rural Benin

Author

Manry, Jeremy, primary, Vincent, Quentin B., additional, Chrabieh, Maya, additional, Lorenzo, Lazaro, additional, Theodorou, Ioannis, additional, Ardant, Marie-Françoise, additional, Johnson, Christian, additional, Marion, Estelle, additional, Chauty, Annick, additional, Marsollier, Laurent, additional, Abel, Laurent, additional, and Alcaïs, Alexandre, additional

Published
2019
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25. A genome wide association study identifies a lncRna as risk factor for pathological inflammatory responses in leprosy

Author

Fava, Vinicius M., primary, Manry, Jeremy, additional, Cobat, Aurélie, additional, Orlova, Marianna, additional, Van Thuc, Nguyen, additional, Moraes, Milton O., additional, Sales-Marques, Carolinne, additional, Stefani, Mariane M. A., additional, Latini, Ana Carla P., additional, Belone, Andrea F., additional, Thai, Vu Hong, additional, Abel, Laurent, additional, Alcaïs, Alexandre, additional, and Schurr, Erwin, additional

Published
2017
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26. Microdeletion on chromosome 8p23.1 in a familial form of severe Buruli ulcer.

Author

Vincent, Quentin B., Belkadi, Aziz, Fayard, Cindy, Marion, Estelle, Adeye, Ambroise, Ardant, Marie-Françoise, Johnson, Christian R., Agossadou, Didier, Lorenzo, Lazaro, Guergnon, Julien, Bole-Feysot, Christine, Manry, Jeremy, Nitschké, Patrick, Theodorou, Ioannis, Casanova, Jean-Laurent, Marsollier, Laurent, Chauty, Annick, Abel, Laurent, Alcaïs, Alexandre, and null, null

Subjects
BURULI ulcer, EPIDEMIOLOGY, PATHOGENIC microorganisms, COMMUNICABLE diseases, MYCOBACTERIUM
Abstract

Buruli ulcer (BU), the third most frequent mycobacteriosis worldwide, is a neglected tropical disease caused by Mycobacterium ulcerans. We report the clinical description and extensive genetic analysis of a consanguineous family from Benin comprising two cases of unusually severe non-ulcerative BU. The index case was the most severe of over 2,000 BU cases treated at the Centre de Dépistage et de Traitement de la Lèpre et de l’Ulcère de Buruli, Pobe, Benin, since its opening in 2003. The infection spread to all limbs with PCR-confirmed skin, bone and joint infections. Genome-wide linkage analysis of seven family members was performed and whole-exome sequencing of both patients was obtained. A 37 kilobases homozygous deletion confirmed by targeted resequencing and located within a linkage region on chromosome 8 was identified in both patients but was absent from unaffected siblings. We further assessed the presence of this deletion on genotyping data from 803 independent local individuals (402 BU cases and 401 BU-free controls). Two BU cases were predicted to be homozygous carriers while none was identified in the control group. The deleted region is located close to a cluster of beta-defensin coding genes and contains a long non-coding (linc) RNA gene previously shown to display highest expression values in the skin. This first report of a microdeletion co-segregating with severe BU in a large family supports the view of a key role of human genetics in the natural history of the disease. [ABSTRACT FROM AUTHOR]

Published
2018
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29. Uniparental Markers in Italy Reveal a Sex-Biased Genetic Structure and Different Historical Strata

Author

Boattini, Alessio, Martinez-Cruz, Begoña, Sarno, Stefania, Harmant, Christine, Useli, Antonella, Sanz, Paula, Yang-Yao, Daniele, Manry, Jeremy, Ciani, Graziella, Luiselli, Donata, Quintana-Murci, Lluis, Comas, David, and Pettener, Davide

Subjects
GENETIC markers, LANDSCAPES, Y chromosome, BIOLOGICAL evolution, POPULATION genetics, HUMAN genetics
Abstract

Located in the center of the Mediterranean landscape and with an extensive coastal line, the territory of what is today Italy has played an important role in the history of human settlements and movements of Southern Europe and the Mediterranean Basin. Populated since Paleolithic times, the complexity of human movements during the Neolithic, the Metal Ages and the most recent history of the two last millennia (involving the overlapping of different cultural and demic strata) has shaped the pattern of the modern Italian genetic structure. With the aim of disentangling this pattern and understanding which processes more importantly shaped the distribution of diversity, we have analyzed the uniparentally-inherited markers in ∼900 individuals from an extensive sampling across the Italian peninsula, Sardinia and Sicily. Spatial PCAs and DAPCs revealed a sex-biased pattern indicating different demographic histories for males and females. Besides the genetic outlier position of Sardinians, a North West–South East Y-chromosome structure is found in continental Italy. Such structure is in agreement with recent archeological syntheses indicating two independent and parallel processes of Neolithisation. In addition, date estimates pinpoint the importance of the cultural and demographic events during the late Neolithic and Metal Ages. On the other hand, mitochondrial diversity is distributed more homogeneously in agreement with older population events that might be related to the presence of an Italian Refugium during the last glacial period in Europe. [ABSTRACT FROM AUTHOR]

Published
2013
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31. Autoantibodies against type I IFNs in patients with critical influenza pneumonia.

Author

Zhang Q, Pizzorno A, Miorin L, Bastard P, Gervais A, Le Voyer T, Bizien L, Manry J, Rosain J, Philippot Q, Goavec K, Padey B, Cupic A, Laurent E, Saker K, Vanker M, Särekannu K, García-Salum T, Ferres M, Le Corre N, Sánchez-Céspedes J, Balsera-Manzanero M, Carratala J, Retamar-Gentil P, Abelenda-Alonso G, Valiente A, Tiberghien P, Zins M, Debette S, Meyts I, Haerynck F, Castagnoli R, Notarangelo LD, Gonzalez-Granado LI, Dominguez-Pinilla N, Andreakos E, Triantafyllia V, Rodríguez-Gallego C, Solé-Violán J, Ruiz-Hernandez JJ, Rodríguez de Castro F, Ferreres J, Briones M, Wauters J, Vanderbeke L, Feys S, Kuo CY, Lei WT, Ku CL, Tal G, Etzioni A, Hanna S, Fournet T, Casalegno JS, Queromes G, Argaud L, Javouhey E, Rosa-Calatrava M, Cordero E, Aydillo T, Medina RA, Kisand K, Puel A, Jouanguy E, Abel L, Cobat A, Trouillet-Assant S, García-Sastre A, and Casanova JL

Subjects
COVID-19 complications, COVID-19 immunology, Humans, Yellow Fever Vaccine adverse effects, Autoantibodies, Influenza, Human complications, Influenza, Human immunology, Interferon Type I immunology, Interferon Type I metabolism, Pneumonia complications, Pneumonia immunology
Abstract

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old., (© 2022 Zhang et al.)

Published
2022
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32. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

Author

Matuozzo D, Talouarn E, Marchal A, Manry J, Seeleuthner Y, Zhang Y, Bolze A, Chaldebas M, Milisavljevic B, Zhang P, Gervais A, Bastard P, Asano T, Bizien L, Barzaghi F, Abolhassani H, Tayoun AA, Aiuti A, Darazam IA, Allende LM, Alonso-Arias R, Arias AA, Aytekin G, Bergman P, Bondesan S, Bryceson YT, Bustos IG, Cabrera-Marante O, Carcel S, Carrera P, Casari G, Chaïbi K, Colobran R, Condino-Neto A, Covill LE, El Zein L, Flores C, Gregersen PK, Gut M, Haerynck F, Halwani R, Hancerli S, Hammarström L, Hatipoğlu N, Karbuz A, Keles S, Kyheng C, Leon-Lopez R, Franco JL, Mansouri D, Martinez-Picado J, Akcan OM, Migeotte I, Morange PE, Morelle G, Martin-Nalda A, Novelli G, Novelli A, Ozcelik T, Palabiyik F, Pan-Hammarström Q, Pérez de Diego R, Planas-Serra L, Pleguezuelo DE, Prando C, Pujol A, Reyes LF, Rivière JG, Rodriguez-Gallego C, Rojas J, Rovere-Querini P, Schlüter A, Shahrooei M, Sobh A, Soler-Palacin P, Tandjaoui-Lambiotte Y, Tipu I, Tresoldi C, Troya J, van de Beek D, Zatz M, Zawadzki P, Al-Muhsen SZ, Baris-Feldman H, Butte MJ, Constantinescu SN, Cooper MA, Dalgard CL, Fellay J, Heath JR, Lau YL, Lifton RP, Maniatis T, Mogensen TH, von Bernuth H, Lermine A, Vidaud M, Boland A, Deleuze JF, Nussbaum R, Kahn-Kirby A, Mentre F, Tubiana S, Gorochov G, Tubach F, Hausfater P, Meyts I, Zhang SY, Puel A, Notarangelo LD, Boisson-Dupuis S, Su HC, Boisson B, Jouanguy E, Casanova JL, Zhang Q, Abel L, and Cobat A

Abstract

Background: We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases., Methods: We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis., Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7 , with an OR of 27.68 (95%CI:1.5-528.7, P= 1.1×10 -4 ), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2], P= 2.1×10 -4 ). Adding the recently reported TYK2 COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4]; P= 3.4×10 -3 ). When these 14 loci and TLR7 were considered, all individuals hemizygous ( n =20) or homozygous ( n =5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0], P =4.7×10 -7 ), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9], P =0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P= 1.68×10 -5 )., Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Published
2022
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33. The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

Author

Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Michailidis E, Hoffmann HH, Eto S, Garcia-Prat M, Bizien L, Parra-Martínez A, Yang R, Haljasmägi L, Migaud M, Särekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garçon P, Rivière JG, Lagier JC, Gentile S, Rosen L, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Mégarbane B, Triantafyllia V, Fekkar A, Heath J, Franco J, Anaya JM, Solé-Violán J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte O, Zhang Y, Snow A, Holland S, Biggs C, Moncada-Vélez M, Arias A, Lorenzo L, Boucherit S, Anglicheau D, Planas A, Haerynck F, Duvlis S, Nussbaum R, Ozcelik T, Keles S, Bousfiha A, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarstrom Q, Hammarstrom L, Dupont A, Kurolap A, Metz C, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros L, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye S, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann N, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes L, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig M, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer A, Kennelly S, Bourke N, Halwani R, Sharif-Askari F, Dorgham K, Sallette J, Mehlal-Sedkaoui S, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh D, Erikstrup C, Condino-Neto A, Prando C, Bondarenko A, Spaan A, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton R, Mane S, Anderson M, Boisson B, Béziat V, Zhang SY, Andreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, deLamballerie X, Burdet C, Bouadma L, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen P, Rodríguez-Gallego C, Piemonti L, Notarangelo L, Su H, Kisand K, Okada S, Puel A, Jouanguy E, Rice C, Tiberghien P, Zhang Q, Casanova JL, Abel L, and Cobat A

Abstract

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

Published
2022
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34. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Author

Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ŞN, Rodríguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C, Snow AL, Dalgard CL, Milner JD, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli MJ, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, and Casanova JL

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Asymptomatic Infections, Betacoronavirus, COVID-19, Child, Child, Preschool, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Infant, Interferon Regulatory Factor-7 deficiency, Interferon Regulatory Factor-7 genetics, Male, Middle Aged, Pandemics, Receptor, Interferon alpha-beta deficiency, Receptor, Interferon alpha-beta genetics, SARS-CoV-2, Toll-Like Receptor 3 deficiency, Toll-Like Receptor 3 genetics, Young Adult, Coronavirus Infections genetics, Coronavirus Infections immunology, Interferon Type I immunology, Loss of Function Mutation, Pneumonia, Viral genetics, Pneumonia, Viral immunology
Abstract

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Published
2020
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