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1. Neutralizing IFN-γ autoantibodies are rare and pathogenic in HLA-DRB1*15:02 or 16:02 individuals.

Author

Peel, Jessica, Yang, Rui, Le Voyer, Tom, Gervais, Adrian, Rosain, Jérémie, Bastard, Paul, Behere, Anish, Cederholm, Axel, Bodansky, Aaron, Seeleuthner, Yoann, Conil, Clément, Ding, Jing-Ya, Lei, Wei-Te, Bizien, Lucy, Soudee, Camille, Migaud, Mélanie, Ogishi, Masato, Yatim, Ahmad, Lee, Danyel, Bohlen, Jonathan, Perpoint, Thomas, Perez, Laura, Messina, Fernando, Genet, Roxana, Karkowski, Ludovic, Blot, Mathieu, Lafont, Emmanuel, Toullec, Laurie, Goulvestre, Claire, Mehlal-Sedkaoui, Souad, Sallette, Jérôme, Martin, Fernando, Puel, Anne, Jouanguy, Emmanuelle, Anderson, Mark, Landegren, Nils, Tiberghien, Pierre, Abel, Laurent, Boisson-Dupuis, Stéphanie, Bustamante, Jacinta, Ku, Cheng-Lung, and Casanova, Jean-Laurent

Subjects
Autoimmune diseases, Cytokines, Genetics, Immunology, Adult, Humans, Autoantibodies, Autoimmune Diseases, Genetic Predisposition to Disease, Genotype, HLA-DRB1 Chains, Mycobacterium Infections, Nontuberculous
Abstract

BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe 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) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Unions Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour lenfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea & Bowery Advisory Group, William E. Ford, General Atlantics Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantics Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste daccueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS).

Published
2024

2. Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

Author

Sharma, Mehul, Leung, Daniel, Momenilandi, Mana, Jones, Lauren CW, Pacillo, Lucia, James, Alyssa E, Murrell, Jill R, Delafontaine, Selket, Maimaris, Jesmeen, Vaseghi-Shanjani, Maryam, Del Bel, Kate L, Lu, Henry Y, Chua, Gilbert T, Di Cesare, Silvia, Fornes, Oriol, Liu, Zhongyi, Di Matteo, Gigliola, Fu, Maggie P, Amodio, Donato, San Tam, Issan Yee, Chan, Gavin Shueng Wai, Sharma, Ashish A, Dalmann, Joshua, van der Lee, Robin, Blanchard-Rohner, Géraldine, Lin, Susan, Philippot, Quentin, Richmond, Phillip A, Lee, Jessica J, Matthews, Allison, Seear, Michael, Turvey, Alexandra K, Philips, Rachael L, Brown-Whitehorn, Terri F, Gray, Christopher J, Izumi, Kosuke, Treat, James R, Wood, Kathleen H, Lack, Justin, Khleborodova, Asya, Niemela, Julie E, Yang, Xingtian, Liang, Rui, Kui, Lin, Wong, Christina Sze Man, Poon, Grace Wing Kit, Hoischen, Alexander, van der Made, Caspar I, Yang, Jing, Chan, Koon Wing, Da Rosa Duque, Jaime Sou, Lee, Pamela Pui Wah, Ho, Marco Hok Kung, Chung, Brian Hon Yin, Le, Huong Thi Minh, Yang, Wanling, Rohani, Pejman, Fouladvand, Ali, Rokni-Zadeh, Hassan, Changi-Ashtiani, Majid, Miryounesi, Mohammad, Puel, Anne, Shahrooei, Mohammad, Finocchi, Andrea, Rossi, Paolo, Rivalta, Beatrice, Cifaldi, Cristina, Novelli, Antonio, Passarelli, Chiara, Arasi, Stefania, Bullens, Dominique, Sauer, Kate, Claeys, Tania, Biggs, Catherine M, Morris, Emma C, Rosenzweig, Sergio D, O’Shea, John J, Wasserman, Wyeth W, Bedford, H Melanie, van Karnebeek, Clara DM, Palma, Paolo, Burns, Siobhan O, Meyts, Isabelle, Casanova, Jean-Laurent, Lyons, Jonathan J, Parvaneh, Nima, Van Nguyen, Anh Thi, Cancrini, Caterina, Heimall, Jennifer, Ahmed, Hanan, McKinnon, Margaret L, Lau, Yu Lung, Béziat, Vivien, and Turvey, Stuart E

Subjects
Genetics, Rare Diseases, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Humans, STAT6 Transcription Factor, Gain of Function Mutation, Asthma, Food Hypersensitivity, Immunoglobulin E, Medical and Health Sciences, Immunology
Abstract

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Published
2023

3. Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

Author

Casanova, Jean-Laurent and Anderson, Mark S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Immunology, Pneumonia & Influenza, Infectious Diseases, Clinical Research, Pediatric, Pneumonia, Emerging Infectious Diseases, Genetics, Lung, Prevention, Biodefense, Vaccine Related, Autoimmune Disease, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Humans, COVID-19, SARS-CoV-2, Interferon Type I, Virus Diseases, Autoantibodies, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Since 2003, rare inborn errors of human type I IFN immunity have been discovered, each underlying a few severe viral illnesses. Autoantibodies neutralizing type I IFNs due to rare inborn errors of autoimmune regulator (AIRE)-driven T cell tolerance were discovered in 2006, but not initially linked to any viral disease. These two lines of clinical investigation converged in 2020, with the discovery that inherited and/or autoimmune deficiencies of type I IFN immunity accounted for approximately 15%-20% of cases of critical COVID-19 pneumonia in unvaccinated individuals. Thus, insufficient type I IFN immunity at the onset of SARS-CoV-2 infection may be a general determinant of life-threatening COVID-19. These findings illustrate the unpredictable, but considerable, contribution of the study of rare human genetic diseases to basic biology and public health.

Published
2023

4. Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq.

Author

Vazquez, Sara E, Mann, Sabrina A, Bodansky, Aaron, Kung, Andrew F, Quandt, Zoe, Ferré, Elise MN, Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y, Tagi, Veronica M, Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R, Kämpe, Olle, Dobbs, Kerry, Delmonte, Ottavia M, Bacchetta, Rosa, Notarangelo, Luigi D, Burns, Jane C, Casanova, Jean-Laurent, Lionakis, Michail S, Torgerson, Troy R, Anderson, Mark S, and DeRisi, Joseph L

Subjects
Humans, Bacteriophages, Autoimmune Diseases, Homeodomain Proteins, Proteome, Autoantibodies, Autoantigens, Immunoprecipitation, Autoimmunity, COVID-19, APS1, IPEX, PhIP-seq, autoantibody, autoantigen, human, immunology, inflammation, Autoimmune Disease, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Human, Biochemistry and Cell Biology
Abstract

Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.

Published
2022

5. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19

Author

van der Wijst, Monique GP, Vazquez, Sara E, Hartoularos, George C, Bastard, Paul, Grant, Tianna, Bueno, Raymund, Lee, David S, Greenland, John R, Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Mann, Sabrina A, Lynch, Kara L, Yun, Cassandra, Havlir, Diane V, Chamie, Gabriel, Marquez, Carina, Greenhouse, Bryan, Lionakis, Michail S, Norris, Philip J, Dumont, Larry J, Kelly, Kathleen, Zhang, Peng, Zhang, Qian, Gervais, Adrian, Le Voyer, Tom, Whatley, Alexander, Si, Yichen, Byrne, Ashley, Combes, Alexis J, Rao, Arjun Arkal, Song, Yun S, Fragiadakis, Gabriela K, Kangelaris, Kirsten, Calfee, Carolyn S, Erle, David J, Hendrickson, Carolyn, Krummel, Matthew F, Woodruff, Prescott G, Langelier, Charles R, Casanova, Jean-Laurent, Derisi, Joseph L, Anderson, Mark S, Ye, Chun Jimmie, consortium, on behalf of the UCSF COMET, Abe-Jones, Yumiko, Alvarenga, Bonny, Asthana, Saurabh, Beagle, Alexander, Bhakta, Tanvi, Bhide, Sharvari, Cai, Cathy, Calvo, Maria, Carrillo, Sidney A, Chak, Suzanna, Collins, Zachary, Dandekar, Ravi, Darmanis, Spyros, Esmaili, Armond, Ghale, Rajani, Giberson, Jeremy, Glenn, Pat, Gonzalez, Ana, Jauregui, Alejandra, Jones, Norman, Ke, Serena, Lea, Tasha, Lee, Deanna, Lelidowicz, Aleskandra, Liu, Kathleen, Lota, Raphael, Matthay, Michael, Milush, Jeff, Nguyen, Viet, Nigam, Nishita, Ortiz, Gabe, Pierce, Logan, Prasad, Priya, Rajan, Jayant, Rashid, Ahmad Sadeed, Rodriguez, Nicklaus, Samad, Bushra, Scarlet, Diane, Shaw, Cole, Sigman, Austin, Sinha, Pratik, Spitzer, Matthew, Tang, Kevin, Altamirano, Luz Torres, Tumurbaatar, Erden, Willmore, Andrew, Wilson, Michael, Withers, Reese, Yee, Kimberly, Zamecnik, Colin, Zhan, Jenny, and Zhou, Mingyue

Subjects
Biomedical and Clinical Sciences, Immunology, Coronaviruses, Clinical Research, Emerging Infectious Diseases, Genetics, Infectious Diseases, Lung, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Autoantibodies, COVID-19, Humans, Interferon Type I, UCSF COMET consortium, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.

Published
2021

6. Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance

Author

Asano, Takaki, Khourieh, Joëlle, Zhang, Peng, Rapaport, Franck, Spaan, András N, Li, Juan, Lei, Wei-Te, Pelham, Simon J, Hum, David, Chrabieh, Maya, Han, Ji Eun, Guérin, Antoine, Mackie, Joseph, Gupta, Sudhir, Saikia, Biman, Baghdadi, Jamila EI, Fadil, Ilham, Bousfiha, Aziz, Habib, Tanwir, Marr, Nico, Ganeshanandan, Luckshman, Peake, Jane, Droney, Luke, Williams, Andrew, Celmeli, Fatih, Hatipoglu, Nevin, Ozcelik, Tayfun, Picard, Capucine, Abel, Laurent, Tangye, Stuart G, Boisson-Dupuis, Stéphanie, Zhang, Qian, Puel, Anne, Béziat, Vivien, Casanova, Jean-Laurent, and Boisson, Bertrand

Subjects
Rare Diseases, Genetics, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Alleles, Alternative Splicing, Child, Child, Preschool, Codon, Nonsense, Evolution, Molecular, Family, Female, Frameshift Mutation, Genes, Dominant, Genetics, Population, HEK293 Cells, Humans, Infant, Infant, Newborn, Job Syndrome, Male, Middle Aged, Mutation, Pedigree, Protein Biosynthesis, RNA, Messenger, STAT3 Transcription Factor, Medical and Health Sciences, Immunology
Abstract

Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) carry rare heterozygous STAT3 variants. Only six of the 135 in-frame variants reported have been experimentally shown to be dominant negative (DN), and it has been recently suggested that eight out-of-frame variants operate by haploinsufficiency. We experimentally tested these 143 variants, 7 novel out-of-frame variants found in HIES patients, and other STAT3 variants from the general population. Strikingly, all 15 out-of-frame variants were DN via their encoded (1) truncated proteins, (2) neoproteins generated from a translation reinitiation codon, and (3) isoforms from alternative transcripts or a combination thereof. Moreover, 128 of the 135 in-frame variants (95%) were also DN. The patients carrying the seven non-DN STAT3 in-frame variants have not been studied for other genetic etiologies. Finally, none of the variants from the general population tested, including an out-of-frame variant, were DN. Overall, our findings show that heterozygous STAT3 variants, whether in or out of frame, underlie AD-HIES through negative dominance rather than haploinsufficiency.

Published
2021

7. Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1

Author

Bastard, Paul, Orlova, Elizaveta, Sozaeva, Leila, Lévy, Romain, James, Alyssa, Schmitt, Monica M, Ochoa, Sebastian, Kareva, Maria, Rodina, Yulia, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Neehus, Anna-Lena, Shaw, Elana, Migaud, Mélanie, Bizien, Lucy, Ekwall, Olov, Berg, Stefan, Beccuti, Guglielmo, Ghizzoni, Lucia, Thiriez, Gérard, Pavot, Arthur, Goujard, Cécile, Frémond, Marie-Louise, Carter, Edwin, Rothenbuhler, Anya, Linglart, Agnès, Mignot, Brigite, Comte, Aurélie, Cheikh, Nathalie, Hermine, Olivier, Breivik, Lars, Husebye, Eystein S, Humbert, Sébastien, Rohrlich, Pierre, Coaquette, Alain, Vuoto, Fanny, Faure, Karine, Mahlaoui, Nizar, Kotnik, Primož, Battelino, Tadej, Podkrajšek, Katarina Trebušak, Kisand, Kai, Ferré, Elise MN, DiMaggio, Thomas, Rosen, Lindsey B, Burbelo, Peter D, McIntyre, Martin, Kann, Nelli Y, Shcherbina, Anna, Pavlova, Maria, Kolodkina, Anna, Holland, Steven M, Zhang, Shen-Ying, Crow, Yanick J, Notarangelo, Luigi D, Su, Helen C, Abel, Laurent, Anderson, Mark S, Jouanguy, Emmanuelle, Neven, Bénédicte, Puel, Anne, Casanova, Jean-Laurent, and Lionakis, Michail S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Infectious Diseases, Rare Diseases, Pneumonia, Pneumonia & Influenza, Autoimmune Disease, Clinical Research, Lung, Adolescent, Adult, Autoantibodies, COVID-19, Child, Female, Humans, Interferon Type I, Male, Middle Aged, Polyendocrinopathies, Autoimmune, SARS-CoV-2, Young Adult, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.

Published
2021

8. Immigration in science

Author

Casanova, Jean-Laurent, Holtzman, David M, Kaech, Susan M, Lanier, Lewis L, Nathan, Carl F, Rudensky, Alexander Y, Tuveson, David, and Wolchok, Jedd D

Subjects
Biomedical and Clinical Sciences, Health Sciences, Emigrants and Immigrants, Emigration and Immigration, Humans, Laboratories, Leadership, Motivation, Research, Research Personnel, United States, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

The advance of science is dependent upon collaboration, which does not have a visa attached to it. Indeed, over 40% of all American-based Nobel Prize winners are immigrants, and data from the National Science Foundation show that 49% of postdocs and 29% of science and engineering faculty in the US are foreign-born. However, restrictive new immigration policies in the US have left many scientists deeply concerned about their future and many American-based laboratories worried about attracting the best talent. At JEM, we're celebrating immigration by sharing the experiences of immigrant and nonimmigrant scientists on our editorial board. Alexander Rudensky and Jean-Laurent Casanova give their firsthand perspective on immigrating to the US, while Jedd Wolchok, Carl Nathan, David Holtzman, Susan Kaech, Lewis Lanier, and David Tuveson reflect on how immigration has affected their laboratories.

Published
2020

9. Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome.

Author

Béziat, Vivien, Tavernier, Simon J, Chen, Yin-Huai, Ma, Cindy S, Materna, Marie, Laurence, Arian, Staal, Jens, Aschenbrenner, Dominik, Roels, Lisa, Worley, Lisa, Claes, Kathleen, Gartner, Lisa, Kohn, Lisa A, De Bruyne, Marieke, Schmitz-Abe, Klaus, Charbonnier, Louis-Marie, Keles, Sevgi, Nammour, Justine, Vladikine, Natasha, Maglorius Renkilaraj, Majistor Raj Luxman, Seeleuthner, Yoann, Migaud, Mélanie, Rosain, Jérémie, Jeljeli, Mohamed, Boisson, Bertrand, Van Braeckel, Eva, Rosenfeld, Jill A, Dai, Hongzheng, Burrage, Lindsay C, Murdock, David R, Lambrecht, Bart N, Avettand-Fenoel, Véronique, Vogel, Tiphanie P, Undiagnosed Diseases Network, Esther, Charles R, Haskologlu, Sule, Dogu, Figen, Ciznar, Peter, Boutboul, David, Ouachée-Chardin, Marie, Amourette, Jean, Lebras, Marie-Noëlle, Gauvain, Clément, Tcherakian, Colas, Ikinciogullari, Aydan, Beyaert, Rudi, Abel, Laurent, Milner, Joshua D, Grimbacher, Bodo, Couderc, Louis-Jean, Butte, Manish J, Freeman, Alexandra F, Catherinot, Émilie, Fieschi, Claire, Chatila, Talal A, Tangye, Stuart G, Uhlig, Holm H, Haerynck, Filomeen, Casanova, Jean-Laurent, and Puel, Anne

Subjects
Undiagnosed Diseases Network, Th2 Cells, Cells, Cultured, Cell Membrane, Fibroblasts, Humans, C-Reactive Protein, Cytokines, Pedigree, Genetics, Population, Up-Regulation, Kinetics, Genes, Dominant, Phenotype, Mutation, Alleles, Models, Biological, Adolescent, Middle Aged, Child, Female, Male, Cytokine Receptor gp130, Young Adult, HEK293 Cells, Job Syndrome, Loss of Function Mutation, Cells, Cultured, Genetics, Population, Genes, Dominant, Models, Biological, Medical and Health Sciences, Immunology
Abstract

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients' heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways.

Published
2020

10. Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee.

Author

Tangye, Stuart G, Al-Herz, Waleed, Bousfiha, Aziz, Chatila, Talal, Cunningham-Rundles, Charlotte, Etzioni, Amos, Franco, Jose Luis, Holland, Steven M, Klein, Christoph, Morio, Tomohiro, Ochs, Hans D, Oksenhendler, Eric, Picard, Capucine, Puck, Jennifer, Torgerson, Troy R, Casanova, Jean-Laurent, and Sullivan, Kathleen E

Subjects
IUIS, autoinflammatory disorders, immune dysregulation, inborn errors of immunity, next-generation sequencing, primary immune deficiency, Immunology
Abstract

We report the updated classification of Inborn Errors of Immunity/Primary Immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies. The application of next-generation sequencing continues to expedite the rapid identification of novel gene defects, rare or common; broaden the immunological and clinical phenotypes of conditions arising from known gene defects and even known variants; and implement gene-specific therapies. These advances are contributing to greater understanding of the molecular, cellular, and immunological mechanisms of disease, thereby enhancing immunological knowledge while improving the management of patients and their families. This report serves as a valuable resource for the molecular diagnosis of individuals with heritable immunological disorders and also for the scientific dissection of cellular and molecular mechanisms underlying inborn errors of immunity and related human diseases.

Published
2020

11. Correction to: Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee

Author

Tangye, Stuart G, Al-Herz, Waleed, Bousfiha, Aziz, Chatila, Talal, Cunningham-Rundles, Charlotte, Etzioni, Amos, Franco, Jose Luis, Holland, Steven M, Klein, Christoph, Morio, Tomohiro, Ochs, Hans D, Oksenhendler, Eric, Picard, Capucine, Puck, Jennifer, Torgerson, Troy R, Casanova, Jean-Laurent, and Sullivan, Kathleen E

Subjects
Biomedical and Clinical Sciences, Immunology, Biotechnology
Abstract

The original version of this article unfortunately contained mistakes in reference numbers. The in-text citations and the references were mismatched. The original article has been corrected.

Published
2020

12. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification

Author

Bousfiha, Aziz, Jeddane, Leila, Picard, Capucine, Al-Herz, Waleed, Ailal, Fatima, Chatila, Talal, Cunningham-Rundles, Charlotte, Etzioni, Amos, Franco, Jose Luis, Holland, Steven M, Klein, Christoph, Morio, Tomohiro, Ochs, Hans D, Oksenhendler, Eric, Puck, Jennifer, Torgerson, Troy R, Casanova, Jean-Laurent, Sullivan, Kathleen E, and Tangye, Stuart G

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Autoimmunity, Genotype, Hereditary Autoinflammatory Diseases, Humans, Hypersensitivity, Immunity, Immunologic Deficiency Syndromes, Phenotype, IUIS, primary immune deficiency, inborn errors of immunity, immune dysregulation, autoinflammatory disorders, classification, Immunology
Abstract

Since 2013, the International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) has published an updated phenotypic classification of IEI, which accompanies and complements their genotypic classification into ten tables. This phenotypic classification is user-friendly and serves as a resource for clinicians at the bedside. There are now 430 single-gene IEI underlying phenotypes as diverse as infection, malignancy, allergy, autoimmunity, and autoinflammation. We herein report the 2019 phenotypic classification, including the 65 new conditions. The diagnostic algorithms are based on clinical and laboratory phenotypes for each of the ten broad categories of IEI.

Published
2020

13. An essential role for the Zn2+ transporter ZIP7 in B cell development

Author

Anzilotti, Consuelo, Swan, David J, Boisson, Bertrand, Deobagkar-Lele, Mukta, Oliveira, Catarina, Chabosseau, Pauline, Engelhardt, Karin R, Xu, Xijin, Chen, Rui, Alvarez, Luis, Berlinguer-Palmini, Rolando, Bull, Katherine R, Cawthorne, Eleanor, Cribbs, Adam P, Crockford, Tanya L, Dang, Tarana Singh, Fearn, Amy, Fenech, Emma J, de Jong, Sarah J, Lagerholm, B Christoffer, Ma, Cindy S, Sims, David, van den Berg, Bert, Xu, Yaobo, Cant, Andrew J, Kleiner, Gary, Leahy, T Ronan, de la Morena, M Teresa, Puck, Jennifer M, Shapiro, Ralph S, van der Burg, Mirjam, Chapman, J Ross, Christianson, John C, Davies, Benjamin, McGrath, John A, Przyborski, Stefan, Santibanez Koref, Mauro, Tangye, Stuart G, Werner, Andreas, Rutter, Guy A, Padilla-Parra, Sergi, Casanova, Jean-Laurent, Cornall, Richard J, Conley, Mary Ellen, and Hambleton, Sophie

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Prevention, Genetics, Brain Disorders, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Agammaglobulinemia, Animals, B-Lymphocytes, Cation Transport Proteins, Child, Preschool, Cytosol, Disease Models, Animal, Endoplasmic Reticulum, Female, Gene Expression Profiling, Humans, Infant, Male, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Pedigree, Zinc, Immunology, Biochemistry and cell biology
Abstract

Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn2+ in modulating B cell receptor signal strength and positive selection.

Published
2019

14. Mechanisms of genotype-phenotype correlation in autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency

Author

Petersheim, Daniel, Massaad, Michel J, Lee, Saetbyul, Scarselli, Alessia, Cancrini, Caterina, Moriya, Kunihiko, Sasahara, Yoji, Lankester, Arjan C, Dorsey, Morna, Di Giovanni, Daniela, Bezrodnik, Liliana, Ohnishi, Hidenori, Nishikomori, Ryuta, Tanita, Kay, Kanegane, Hirokazu, Morio, Tomohiro, Gelfand, Erwin W, Jain, Ashish, Secord, Elizabeth, Picard, Capucine, Casanova, Jean-Laurent, Albert, Michael H, Torgerson, Troy R, and Geha, Raif S

Subjects
Genetics, Aetiology, 2.1 Biological and endogenous factors, Carrier Proteins, Chemokine CCL20, Ectodermal Dysplasia, Genetic Diseases, X-Linked, Genotype, HEK293 Cells, Humans, Immunologic Deficiency Syndromes, Intercellular Adhesion Molecule-1, Interleukin-6, NF-KappaB Inhibitor alpha, NF-kappa B p52 Subunit, Point Mutation, Primary Immunodeficiency Diseases, Proto-Oncogene Mas, Signal Transduction, Ectodermal dysplasia with immune deficiency, NF-kappa B inhibitor alpha, canonical nuclear factor kappa B pathway, noncanonical nuclear factor kappa B pathway, lymphorganogenesis, hematopoietic stem cell transplantation, NF-κB inhibitor α, canonical nuclear factor κB pathway, noncanonical nuclear factor κB pathway, Immunology, Allergy
Abstract

BackgroundAutosomal dominant anhidrotic ectodermal dysplasia with immune deficiency (AD EDA-ID) is caused by heterozygous point mutations at or close to serine 32 and serine 36 or N-terminal truncations in IκBα that impair its phosphorylation and degradation and thus activation of the canonical nuclear factor κ light chain enhancer of activated B cells (NF-κB) pathway. The outcome of hematopoietic stem cell transplantation is poor in patients with AD EDA-ID despite achievement of chimerism. Mice heterozygous for the serine 32I mutation in IκBα have impaired noncanonical NF-κB activity and defective lymphorganogenesis.ObjectiveWe sought to establish genotype-phenotype correlation in patients with AD EDA-ID.MethodsA disease severity scoring system was devised. Stability of IκBα mutants was examined in transfected cells. Immunologic, biochemical, and gene expression analyses were performed to evaluate canonical and noncanonical NF-κB signaling in skin-derived fibroblasts.ResultsDisease severity was greater in patients with IκBα point mutations than in those with truncation mutations. IκBα point mutants were expressed at significantly higher levels in transfectants compared with truncation mutants. Canonical NF-κB-dependent IL-6 secretion and upregulation of the NF-κB subunit 2/p100 and RELB proto-oncogene, NF-κB subunit (RelB) components of the noncanonical NF-κB pathway were diminished significantly more in patients with point mutations compared with those with truncations. Noncanonical NF-κB-driven generation of the transcriptionally active p100 cleavage product p52 and upregulation of CCL20, intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1), which are important for lymphorganogenesis, were diminished significantly more in LPS plus α-lymphotoxin β receptor-stimulated fibroblasts from patients with point mutations compared with those with truncations.ConclusionsIκBα point mutants accumulate at higher levels compared with truncation mutants and are associated with more severe disease and greater impairment of canonical and noncanonical NF-κB activity in patients with AD EDA-ID.

Published
2018

15. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity

Author

Picard, Capucine, Bobby Gaspar, H, Al-Herz, Waleed, Bousfiha, Aziz, Casanova, Jean-Laurent, Chatila, Talal, Crow, Yanick J, Cunningham-Rundles, Charlotte, Etzioni, Amos, Franco, Jose Luis, Holland, Steven M, Klein, Christoph, Morio, Tomohiro, Ochs, Hans D, Oksenhendler, Eric, Puck, Jennifer, Tang, Mimi LK, Tangye, Stuart G, Torgerson, Troy R, and Sullivan, Kathleen E

Subjects
Inflammatory and immune system, Allergy and Immunology, Humans, Immunity, Immunologic Deficiency Syndromes, Research Report, Societies, Scientific, World Health Organization, IUIS, primary immune deficiency, immune dysregulation, autoinflammatory disorders, Immunology
Abstract

Beginning in 1970, a committee was constituted under the auspices of the World Health Organization (WHO) to catalog primary immunodeficiencies. Twenty years later, the International Union of Immunological Societies (IUIS) took the remit of this committee. The current report details the categorization and listing of 354 (as of February 2017) inborn errors of immunity. The growth and increasing complexity of the field have been impressive, encompassing an increasing variety of conditions, and the classification described here will serve as a critical reference for immunologists and researchers worldwide.

Published
2018

16. The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies

Author

Bousfiha, Aziz, Jeddane, Leïla, Picard, Capucine, Ailal, Fatima, Bobby Gaspar, H, Al-Herz, Waleed, Chatila, Talal, Crow, Yanick J, Cunningham-Rundles, Charlotte, Etzioni, Amos, Franco, Jose Luis, Holland, Steven M, Klein, Christoph, Morio, Tomohiro, Ochs, Hans D, Oksenhendler, Eric, Puck, Jennifer, Tang, Mimi LK, Tangye, Stuart G, Torgerson, Troy R, Casanova, Jean-Laurent, and Sullivan, Kathleen E

Subjects
Biomedical and Clinical Sciences, Immunology, Genetics, Prevention, Inflammatory and immune system, Allergy and Immunology, Humans, Immunity, Immunologic Deficiency Syndromes, International Cooperation, Phenotype, Primary immunodeficiencies, Classification, Phenotypic, IUIS, Inborn errors of immunity
Abstract

Since the 1990s, the International Union of Immunological Societies (IUIS) PID expert committee (EC), now called Inborn Errors of Immunity Committee, has published every other year a classification of the inborn errors of immunity. This complete catalog serves as a reference for immunologists and researchers worldwide. However, it was unadapted for clinicians at the bedside. For those, the IUIS PID EC is now publishing a phenotypical classification since 2013, which proved to be more user-friendly. There are now 320 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. We herein propose the revised 2017 phenotypic classification, based on the accompanying 2017 IUIS Inborn Errors of Immunity Committee classification.

Published
2018

17. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.

Author

MacDuff, Donna A, Reese, Tiffany A, Kimmey, Jacqueline M, Weiss, Leslie A, Song, Christina, Zhang, Xin, Kambal, Amal, Duan, Erning, Carrero, Javier A, Boisson, Bertrand, Laplantine, Emmanuel, Israel, Alain, Picard, Capucine, Colonna, Marco, Edelson, Brian T, Sibley, L David, Stallings, Christina L, Casanova, Jean-Laurent, Iwai, Kazuhiro, and Virgin, Herbert W

Subjects
Bone Marrow Cells, Macrophages, Animals, Mice, Knockout, Humans, Mice, Toxoplasma, Citrobacter, Mycobacterium tuberculosis, Listeria monocytogenes, Herpesviridae, Rhadinovirus, Herpesviridae Infections, Immunologic Deficiency Syndromes, Acute Disease, Chronic Disease, Inflammation, Caspase 1, Ubiquitin-Protein Ligases, Inflammation Mediators, Interleukin-6, Cytokines, Genetic Complementation Test, Cell Compartmentation, Phenotype, Immunity, Innate, Listeriosis, NF-kappaB, immunodeficiency, immunology, infectious disease, linear ubiquitination, microbiology, mouse, murine gamma-herpesvirus 68, Immunity, Innate, Knockout, Biochemistry and Cell Biology
Abstract

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.

Published
2015

18. Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

Author

Al-Herz, Waleed, Bousfiha, Aziz, Casanova, Jean-Laurent, Chatila, Talal, Conley, Mary Ellen, Cunningham-Rundles, Charlotte, Etzioni, Amos, Franco, Jose Luis, Gaspar, H Bobby, Holland, Steven M, Klein, Christoph, Nonoyama, Shigeaki, Ochs, Hans D, Oksenhendler, Erik, Picard, Capucine, Puck, Jennifer M, Sullivan, Kate, and Tang, Mimi LK

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pediatric, Genetics, Rare Diseases, Inflammatory and immune system, Good Health and Well Being, primary immunodeficiencies, IUIS, classification, genetic defects, genotype, Immunology, Medical Microbiology, Biochemistry and cell biology
Abstract

We report the updated classification of primary immunodeficiencies (PIDs) compiled by the Expert Committee of the International Union of Immunological Societies. In comparison to the previous version, more than 30 new gene defects are reported in this updated version. In addition, we have added a table of acquired defects that are phenocopies of PIDs. For each disorder, the key clinical and laboratory features are provided. This classification is the most up-to-date catalog of all known PIDs and acts as a current reference of the knowledge of these conditions and is an important aid for the molecular diagnosis of patients with these rare diseases.

Published
2014

19. Corrigendum: Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

Author

Al-Herz, Waleed, Bousfiha, Aziz, Casanova, Jean-Laurent, Chatila, Talal, Conley, Mary Ellen, Cunningham-Rundles, Charlotte, Etzioni, Amos, Franco, Jose Luis, Gaspar, H Bobby, Holland, Steven M, Klein, Christoph, Nonoyama, Shigeaki, Ochs, Hans D, Oksenhendler, Erik, Picard, Capucine, Puck, Jennifer M, Sullivan, Kate, and Tang, Mimi LK

Subjects
Biomedical and Clinical Sciences, Immunology, immunodeficiency, classification, gene defects, genotype, IUIS, Medical Microbiology, Biochemistry and cell biology, Genetics
Abstract

[This corrects the article on p. 162 in vol. 5, PMID: 24795713.].

Published
2014

20. A Phenotypic Approach for IUIS PID Classification and Diagnosis: Guidelines for Clinicians at the Bedside

Author

Bousfiha, Ahmed Aziz, Jeddane, Leïla, Ailal, Fatima, Al Herz, Waleed, Conley, Mary Ellen, Cunningham-Rundles, Charlotte, Etzioni, Amos, Fischer, Alain, Franco, Jose Luis, Geha, Raif S, Hammarström, Lennart, Nonoyama, Shigeaki, Ochs, Hans D, Roifman, Chaim M, Seger, Reinhard, Tang, Mimi LK, Puck, Jennifer M, Chapel, Helen, Notarangelo, Luigi D, and Casanova, Jean-Laurent

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pediatric, Clinical Research, Algorithms, Diagnosis, Differential, Diagnostic Tests, Routine, Genotype, Humans, Immunologic Deficiency Syndromes, Immunologic Tests, Phenotype, Practice Guidelines as Topic, Primary immunodeficiency, classification, IUIS, diagnosis tool, Immunology
Abstract

The number of genetically defined Primary Immunodeficiency Diseases (PID) has increased exponentially, especially in the past decade. The biennial classification published by the IUIS PID expert committee is therefore quickly expanding, providing valuable information regarding the disease-causing genotypes, the immunological anomalies, and the associated clinical features of PIDs. These are grouped in eight, somewhat overlapping, categories of immune dysfunction. However, based on this immunological classification, the diagnosis of a specific PID from the clinician's observation of an individual clinical and/or immunological phenotype remains difficult, especially for non-PID specialists. The purpose of this work is to suggest a phenotypic classification that forms the basis for diagnostic trees, leading the physician to particular groups of PIDs, starting from clinical features and combining routine immunological investigations along the way. We present 8 colored diagnostic figures that correspond to the 8 PID groups in the IUIS Classification, including all the PIDs cited in the 2011 update of the IUIS classification and most of those reported since.

Published
2013

21. Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

Author

Al-Herz, Waleed, Bousfiha, Aziz, Casanova, Jean-Laurent, Chapel, Helen, Conley, Mary Ellen, Cunningham-Rundles, Charlotte, Etzioni, Amos, Fischer, Alain, Franco, Jose Luis, Geha, Raif S, Hammarström, Lennart, Nonoyama, Shigeaki, Notarangelo, Luigi Daniele, Ochs, Hans Dieter, Puck, Jennifer M, Roifman, Chaim M, Seger, Reinhard, and Tang, Mimi LK

Subjects
Biomedical and Clinical Sciences, Immunology, Rare Diseases, Good Health and Well Being, primary immunodeficiency diseases, Medical Microbiology, Biochemistry and cell biology, Genetics
Abstract

We report the updated classification of primary immunodeficiency diseases, compiled by the ad hoc Expert Committee of the International Union of Immunological Societies. As compared to the previous edition, more than 15 novel disease entities have been added in the updated version. For each disorders, the key clinical and laboratory features are provided. This updated classification is meant to help in the diagnostic approach to patients with these diseases.

Published
2011

24. Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia

Author

García-García, Ana, Pérez de Diego, Rebeca, Flores, Carlos, Rinchai, Darawan, Solé-Violán, Jordi, Deyà-Martínez, Àngela, García-Solis, Blanca, Lorenzo-Salazar, José M., Hernández-Brito, Elisa, Lanz, Anna-Lisa, Moens, Leen, Bucciol, Giorgia, Almuqamam, Mohamed, Domachowske, Joseph B., Colino, Elena, Santos-Perez, Juan Luis, Marco, Francisco M., Pignata, Claudio, Bousfiha, Aziz, Turvey, Stuart E., Bauer, Stefanie, Haerynck, Filomeen, Ocejo-Vinyals, Javier Gonzalo, Lendinez, Francisco, Prader, Seraina, Naumann-Bartsch, Nora, Pachlopnik Schmid, Jana, Biggs, Catherine M., Hildebrand, Kyla, Dreesman, Alexandra, Cárdenes, Miguel Ángel, Ailal, Fatima, Benhsaien, Ibtihal, Giardino, Giuliana, Molina-Fuentes, Agueda, Fortuny, Claudia, Madhavarapu, Swetha, Conway, Daniel H., Prando, Carolina, Schidlowski, Laire, Martínez de Saavedra Álvarez, María Teresa, Alfaro, Rafael, Rodríguez de Castro, Felipe, Kindle, Gerhard, Mahlaoui, Nizar, Seidel, Markus G., Vassilios, Lougaris, Seppänen, Mikko R.J., Abel, Laurent, Aiuti, Alessandro, Al-Muhsen, Saleh, Al-Mulla, Fahd, Anderson, Mark S., Andreakos, Evangelos, Arias, Andrés A., Baris Feldman, Hagit, Belot, Alexandre, Bogunovic, Dusan, Bolze, Alexandre, Bondarenko, Anastasiia, Bousfiha, Ahmed A., Brodin, Petter, Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Casari, Giorgio, Christodoulou, John, Condino-Neto, Antonio, Constantinescu, Stefan N., Cooper, Megan A., Dalgard, Clifton L., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Fellay, Jacques, Franco, José Luis, Froidure, Antoine, Gregersen, Peter K., Grimbacher, Bodo, Hagin, David, Halwani, Rabih, Hammarström, Lennart, Heath, James R., Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Kisand, Kai, Ku, Cheng-Lung, Lau, Yu-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Mansouri, Davood, Meyts, Isabelle, Milner, Joshua D., Mironska, Kristina, Mogensen, Trine H., Morio, Tomohiro, Ng, Lisa F.P., Notarangelo, Luigi D., Novelli, Antonio, Novelli, Giuseppe, O’Farrelly, Cliona, Okada, Satoshi, Okamoto, Keisuke, Ozcelik, Tayfun, Pan-Hammarström, Qiang, Pape, Jean W., Perez de Diego, Rebecca, Perlin, David S., Pesole, Graziano, Planas, Anna M., Pujol, Aurora, Quintana-Murci, Lluis, Ramaswamy, Sathishkumar, Renia, Laurent, Resnick, Igor, Rodríguez-Gallego, Carlos, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänan, Mikko R.J., Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Snow, Andrew L., Soler-Palacín, Pere, Spaan, András N., Tancevski, Ivan, Tangye, Stuart G., Tayoun, Ahmad Abou, Uddin, K M Furkan, Uddin, Mohammed J., van de Beek, Diederik, Vinh, Donald C., von Bernuth, Horst, Wauters, Joost, Zatz, Mayana, Zawadzki, Pawel, Su, Helen C., Casanova, Jean-Laurent, Hauck, Fabian, Puel, Anne, Bastard, Paul, Boisson, Bertrand, Jouanguy, Emmanuelle, Cobat, Aurélie, Zhang, Qian, Alsina, Laia, ESID Registry Working Party, [missing], COVID Human Genetic Effort, [missing], AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Neurology

Subjects
SARS-CoV-2, Immunology, Signal Transducing, COVID-19, Adaptor Proteins, Settore MED/03, Toll-Like Receptor 7, Myeloid Differentiation Factor 88, Medicine and Health Sciences, COVID-19/complications, Immunology and Allergy, Humans, Myeloid Differentiation Factor 88/genetics, Child, Adaptor Proteins, Signal Transducing
Abstract

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia. ispartof: JOURNAL OF EXPERIMENTAL MEDICINE vol:220 issue:5 ispartof: location:United States status: published

Published
2023
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25. Human inherited complete STAT2 deficiency underlies inflammatory viral diseases

Author

Bucciol, Giorgia, Moens, Leen, Ogishi, Masato, Rinchai, Darawan, Matuozzo, Daniela, Momenilandi, Mana, Kerrouche, Nacim, Cale, Catherine M, Treffeisen, Elsa R, Al Salamah, Mohammad, Al-Saud, Bandar K, Lachaux, Alain, Duclaux-Loras, Remi, Meignien, Marie, Bousfiha, Aziz, Benhsaien, Ibtihal, Shcherbina, Anna, Roppelt, Anna, COVID Human Genetic Effort, Gothe, Florian, Houhou-Fidouh, Nadhira, Hackett, Scott J, Bartnikas, Lisa M, Maciag, Michelle C, Alosaimi, Mohammed F, Chou, Janet, Mohammed, Reem W, Freij, Bishara J, Jouanguy, Emmanuelle, Zhang, Shen-Ying, Boisson-Dupuis, Stephanie, Béziat, Vivien, Zhang, Qian, Duncan, Christopher Ja, Hambleton, Sophie, Casanova, Jean-Laurent, and Meyts, Isabelle

Subjects
Innate immunity, Immunology, General Medicine, Influenza, Genetic diseases
Abstract

STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients' cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival. ispartof: J Clin Invest vol:133 issue:12 pages:e168321- ispartof: location:United States status: Published online

Published
2023
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28. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Author

Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, 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, Jesus, 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, Megarbane, 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, 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, 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, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Mehlal Sedkaoui, Souad, AlKhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C., Ostrowski, Sisse Rye, 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, Duval, Xavier, Mentré, 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, Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M., Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, Bigio, Benedetta, de la Chapelle, Aliénor, Chen, Jie, Chrabieh, Maya, Liu, Dana, Nemirowskaya, Yelena, Cruz, Inés Marín, Materna, Marie, Pelet, Sophie, Seeleuthner, Yoann, Thibault, Chloé, Liu, Zhiyong, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Darazam, Ilad Alavi, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, Alkhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Feldman, Hagit Baris, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Bustamante, Jacinta, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Flores, Carlos, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Gut, Marta, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Lima, Edson Jose Adrian Bolanos, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Lye, David C, Magnone, Cinthia, Mansouri, Davood, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morange, Pierre-Emmanuel, Mordacq, Clémence, Morelle, Guillaume, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paz-Artal, Estela, Pedraza, Sigifredo, González Pellecer, Nancy Carolina, Pellegrini, Silvia, de Diego, Rebeca Pérez, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Planas-Serra, Laura, Ploin, Dominique, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie S, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rivet, Nadia, Rivière, Jacques G, Rocamora-Blanch, Gemma, Rodero, Mathieu P, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Gallego, Carlos, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Sediva, Anna, Seijo, Luis, Seminario, Analia Gisela, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Shahrooei, Mohammad, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Soler, Catherine, Soler-Palacín, Pere, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, THORN, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Troya, Jesús, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Danielson, Jeffrey J., Dobbs, Kerry, Kashyap, Anuj, Ding, Li, Dalgard, Clifton L., Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Bettini, Laura Rachele, D’Angio’, Mariella, Beretta, Ilaria, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Batten, Isabella, Reddy, Conor, McElheron, Matt, Noonan, Claire, Connolly, Emma, Fallon, Aoife, Storgaard, Merete, Jørgensen, Sofie, Erikstrup, Christian, Pedersen, Ole Birger, Sørensen, Erik, Mikkelsen, Susan, Dinh, Khoa Manh, Larsen, Margit Anita Hørup, Paulsen, Isabella Worlewenut, Von Stemann, Jakob Hjorth, Hansen, Morten Bagge, Townsend, Liam, Cheallaigh, Cliona Ni, Bergin, Colm, Martin-Loeches, Ignacio, Dunne, Jean, Conlon, Niall, Bourke, Nollaig, O'Farrelly, Cliona, Allavena, Clotilde, Andrejak, Claire, Angoulvant, François, Azoulay, Cecile, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behilill, Sylvie, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bhavsar, Krishna, Bitker, Laurent, Bouadma, Lila, Bouscambert-Duchamp, Maude, Paz, Pauline Caraux, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, d’Ortenzio, Eric, De Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, 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Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul, Fleuren, Lucas, Geijtenbeek, Suzanne Geerlings Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Lim, Endry H.T., van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan A.I., van der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits C.F.J., Schinkel, Michiel, Schultz, Marcus J., Schrauwen, Femke A.P., Schuurmans, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos, Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Al-Muhsen, Saleh, Al-Mulla, Fahd, Arias, Andrés A., Bogunovic, Dusan, Bolze, Alexandre, Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Froidure, Antoine, Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein S., Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Ku, Cheng-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Milner, Joshua D., Mironska, Kristina, Ng, Lisa F.P., Novelli, Antonio, Novelli, Giuseppe, de Diego, Rebeca Perez, Renia, Laurent, Resnick, Igor, Sancho-Shimizu, Vanessa, Seppänen, Mikko R.J., Shahrooei, Mohammed, Slaby, Ondrej, Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., von Bernuth, Horst, Zawadzki, Pawel, Nadif, Rachel, Goldberg, Marcel, Ozguler, Anna, Henny, Joseph, Lemonnier, Sylvie, Coeuret-Pellicer, Mireille, Le Got, Stéphane, Tzourio, Christophe, Dufouil, Carole, Soumaré, Aïcha, Lachaize, Morgane, Fievet, Nathalie, Flaig, Amandine, Martin, Fernando, Bonneaudeau, Brigitte, Cannet, Dorothée, Gallian, Pierre, Jeanne, Michel, Perroquin, Magali, Hamzeh-Cognasse, Hind, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), 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], Hôpital Lariboisière-Fernand-Widal [APHP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro [Lille], Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hospices Civils de Lyon (HCL), 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), Grand Hôpital de l'Est Francilien (GHEF), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Ballanger [Aulnay-sous-Bois], Hôpital Edouard Herriot [CHU - HCL], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Verdier [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, Howard Hughes Medical Institute, Rockefeller University, European Commission, Jeffrey Modell Foundation, Université de Bordeaux, Meath Foundation, National Human Genome Research Institute, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Fondation du Souffle, Instituto de Salud Carlos III, Institut National de la Santé et de la Recherche Médicale, St. Giles Foundation, Ministère des Solidarités et de la Santé, Sorbonne Université, Mutuelle Générale de l'Education Nationale, Conseil Régional Aquitaine, Conseil régional de Bourgogne-Franche-Comté, Meyer Foundation, Fondation de France, National Cancer Institute, European Regional Development Fund, Fundación DISA, Ministero della Salute, ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(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-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), European Project: IdEx Bordeaux (ANR-10-IDEX- 003-02), Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Lii, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicola, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesu, 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-Loui, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R, Franco, José Lui, 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, Moncada-Vélez, Marcela, Arias, Andrés 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, 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, Mateu, 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, Llui, 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, Idri, 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, Jérome, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C, Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bonradenko, Anastasiia, Spaan, András N, Gilardin, Laurent, Fellay, Jacque, Lyonnet, Stanisla, Bilguvar, Kaya, Lifton, Richard P, Mane, Shrikant, Anderson, Mark S, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Vandreakos, Evangelo, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H, Rowen, Lee, Mond, Jame, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, 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, Rodríguez-Gallego, Carlo, Notarangelo, Luigi D, Su, Helen C, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M, Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hiroshima University, Vall d’Hebron Research Institute (VHIR), University of Tartu, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Members of the The Milieu Intérieur Consortium: Laurent Abel1 , Andres Alcover2 , Hugues Aschard2 , Philippe Bousso2 , Nollaig Bourke3 , Petter Brodin4 , Pierre Bruhns2 , Nadine Cerf-Bensussan5 , Ana Cumano2 , Christophe D’Enfert2 , Ludovic Deriano2 , Marie-Agnès Dillies2 , James Di Santo2 , Françoise Dromer2 , Gérard Eberl2 , Jost Enninga2 , Jacques Fellay6 , Ivo Gomperts-Boneca2 , Milena Hasan2 , Gunilla Karlsson Hedestam4 , Serge Hercberg7 , Molly A. Ingersoll2 , Olivier Lantz8 , Rose Anne Kenny3 , Mickaël Ménager5 , Frédérique Michel2 , Hugo Mouquet2 , Cliona O’Farrelly3 , Etienne Patin2 , Sandra Pellegrini2 , Antonio Rausell5 , Frédéric Rieux-Laucat5 , Lars Rogge2 , Magnus Fontes9 , Anavaj Sakuntabhai2 , Olivier Schwartz2 , Benno Schwikowski2 , Spencer Shorte2 , Frédéric Tangy2 , Antoine Toubert10 , Mathilde Touvier12 , Marie-Noëlle Ungeheuer2 , Christophe Zimmer2 , Matthew L. Albert11 , Darragh Duffy2 , Lluis Quintana-Murc, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Ministère des Solidarités et de la Santé (France), National Health and Medical Research Council (Australia), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Michailidis, Eleftherios, García-Prat, Marina, Paul, Stephanie, Metz, Christine N., Barreiros, Lucila, Domínguez-Garrido, Elena, Vidigal, Mateus, Beek, Diederik van der, Stepanovskyy, Yuriy, Tangye, Stuart G., Quintana-Murci, Lluis, Kan, Nelli, Nussenzweig, Michel C., Baris, Hagit N., Dyer, Adam, Bourke, Nollaig, Vinh, Donald C., Spaan, András N., Fellay, Jacques, Mane, Shrikant M., Anderson, MarK S., Andreakos, Evangelos, Haljasmägi, Liis, Mogensen, Trine, Lamballerie, Xavier de, Soler-Palacín, Pere, Martínez-Picado, Javier, Gregersen, Peter K., Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Prost, Nicolas de, Amador-Borrero, Blanco, Troya, Jesús, Rivière, Jacques G., Gentile, Stephanie, Rosen, Lindsey B., Tharaux, Pierre-Louis, Stépanian, Alain, Mégarbane, Bruno, Heath, James R., Franco, José Luis, Anaya, Juan Manuel, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Velez, Marcela, Planas, Anna M., Nussbaum, Robert, Bousfiha, Ahmed Aziz, Ramírez-Santana, Carolina, Intensive care medicine, Internal medicine, AII - Infectious diseases, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Pathology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, Radiology and nuclear medicine, AMS - Rehabilitation & Development, VU University medical center, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, Anesthesiology, APH - Quality of Care, ACS - Heart failure & arrhythmias, Özçelik, Tayfun, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, HUS Inflammation Center, Admin, Oskar, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, 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 - - GENVIR2020 - ANR-20-CE93-0003 - AAPG2020 - VALID, Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19. - - AABIFNCOV2020 - ANR-20-CO11-0001 - COVID-19 - VALID, Program Initiative d’Excellence - IdEx Bordeaux (ANR-10-IDEX- 003-02) - INCOMING, CHU Tenon [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 Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), École pratique des hautes études (EPHE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Neurology, ANS - Neuroinfection & -inflammation, Graduate School, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Bastard, P, Gervais, A, Le Voyer, T, Rosain, J, Philippot, Q, Manry, J, Michailidis, E, Hoffmann, H, 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, C, 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, J, Lagier, J, Gentile, S, Rosen, L, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, P, Sene, D, Stepanian, A, Megarbane, B, Triantafyllia, V, Fekkar, A, Heath, J, Franco, J, Anaya, J, 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, Coulibaly, B, 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-Hammarström, Q, Hammarström, 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, Y, 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, N, Dorgham, K, Sallette, J, Sedkaoui, S, Alkhater, S, Rigo-Bonnin, R, Morandeira, F, Roussel, L, Vinh, D, Ostrowski, S, Condino-Neto, A, Prando, C, Bonradenko, A, Spaan, A, Gilardin, L, Fellay, J, Lyonnet, S, Bilguvar, K, Lifton, R, Mane, S, Anderson, M, Boisson, B, Béziat, V, Zhang, S, Vandreakos, E, Hermine, O, Pujol, A, Peterson, P, Mogensen, T, Rowen, L, Mond, J, Debette, S, de Lamballerie, X, Duval, X, Mentré, F, Zins, M, Soler-Palacin, P, Colobran, R, Gorochov, G, Solanich, X, Susen, S, Martinez-Picado, J, Raoult, D, Vasse, M, Gregersen, P, Piemonti, L, Rodríguez-Gallego, C, Notarangelo, L, Su, H, Kisand, K, Okada, S, Puel, A, Jouanguy, E, Rice, C, Tiberghien, P, Zhang, Q, Cobat, A, Abel, L, Casanova, J, Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), HGID Lab, COVID Clinicians, COVID-STORM Clinicians, NIAID Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, St. James's Hospital, SARS CoV2 Interest group, French COVID Cohort Study Group, Imagine COVID-Group, Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19, Biobank Investigators, COVID Human Genetic Effort, CONSTANCES cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement du Sang study group, Bigio, B., Boucherit, S., de la Chapelle, A., Chen, J., Chrabieh, M., Coulibaly, B., Liu, D., Nemirowskaya, Y., Cruz, I.M., Materna, M., Pelet, S., Seeleuthner, Y., Thibault, C., Liu, Z., Abad, J., Accordino, G., Achille, C., Aguilera-Albesa, S., Aguiló-Cucurull, A., Aiuti, A., Özkan, E.A., Darazam, I.A., Roblero Albisures, J.A., Aldave, J.C., Ramos, M.A., Khan, T.A., Aliberti, A., Nadji, S.A., Alkan, G., Alkhater, S.A., Allardet-Servent, J., Allende, L.M., Alonso-Arias, R., Alshahrani, M.S., Alsina, L., Alyanakian, M.A., Borrero, B.A., Amoura, Z., Antolí, A., Arrestier, R., Aubart, M., Auguet, T., Avramenko, I., Aytekin, G., Azot, A., Bahram, S., Bajolle, F., Baldanti, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Barzagh, F., Basso, S., Bayhan, G.I., Belot, A., Bezrodnik, L., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blázquez-Gamero, D., Bleibtreu, A., Bloomfield, M., Bolivar-Prados, M., Bondarenko, A., Borghesi, A., Borie, R., Botdhlo-Nevers, E., Bousfiha, A.A., Bousquet, A., Boutolleau, D., Bouvattier, C., Boyarchuk, O., Bravais, J., Briones, M.L., Brunner, M.E., Bruno, R., Bueno, MRP, Bukhari, H., Bustamante, J., Cáceres Agra, J.J., Capra, R., Carapito, R., Carrabba, M., Casari, G., Casasnovas, C., Caseris, M., Cassaniti, I., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Catherinot, E., Celik, J.B., Ceschi, A., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Cohen, Y., Colobran, R., Comarmond, C., Combes, A., Comoli, P., Corsico, A.G., Coşkuner, T., Cvetkovski, A., Cyrus, C., Dalmau, D., Danion, F., Darley, D.R., Das, V., Dauby, N., Dauger, S., De Munter, P., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Desguerre, I., Di Sabatino, A., Diehl, J.L., Dobbelaere, S., Domínguez-Garrido, E., Dubost, C., Ekwall, O., Bozdemir, Ş.E., Elnagdy, M.H., Emiroglu, M., Endo, A., Erdeniz, E.H., Aytekin, S.E., Lasa, MPE, Euvrard, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Ferrer, R., Ferreres, J., Flores, C., Francois, B., Fumadó, V., Fung, KSC, Fusco, F., Gagro, A., Solis, B.G., Gaussem, P., Gayretli, Z., Gil-Herrera, J., Gilardin, L., Gatineau, A.G., Girona-Alarcón, M., Cifuentes Godínez, K.A., Goffard, J.C., Gonzales, N., Gonzalez-Granado, L.I., González-Montelongo, R., Guerder, A., Gülhan, B., Gumucio, V.D., Hanitsch, L.G., Gunst, J., Gut, M., Hadjadj, J., Haerynck, F., Halwani, R., Hammarström, L., Hancerli, S., Hariyan, T., Hatipoglu, N., Heppekcan, D., Hernandez-Brito, E., Ho, P.K., Holanda-Peña, M.S., Horcajada, J.P., Hraiech, S., Humbert, L., Hung, IFN, Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jimeno, M.T., Jordan, I., Yüksek, S.K., Kara, Y.B., Karahan, A., Karbuz, A., Yasar, K.K., Kasapcopur, O., Kashimada, K., Keles, S., Demirkol, Y.K., Kido, Y., Kizil, C., Kılıç, A.O., Klocperk, A., Koutsoukou, A., Król, Z.J., Ksouri, H., Kuentz, P., Kwan, AMC, Kwan, YWM, Kwok, JSY, Lagier, J.C., Lam, DSY, Lampropoulou, V., Lanternier, F., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Lilleri, D., Lima, EJAB, Linglart, A., López-Collazo, E., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Lung, K.C., Luyt, C.E., Lye, D.C., Magnone, C., Mansouri, D., Marchioni, E., Marioli, C., Marjani, M., Marques, L., Pereira, J.M., Martín-Nalda, A., Pueyo, D.M., Martinez-Picado, J., Marzana, I., Mata-Martínez, C., Mathian, A., Matos, L.R., Matthews, G.V., Mayaux, J., McLaughlin-Garcia, R., Meersseman, P., Mège, J.L., Mekontso-Dessap, A., Melki, I., Meloni, F., Meritet, J.F., Merlani, P., Akcan, Ö.M., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Million, M., Mirault, T., Mircher, C., Mirsaeidi, M., Mizoguchi, Y., Modi, B.P., Mojoli, F., Moncomble, E., Melián, A.M., Martinez, A.M., Morandeira, F., Morange, P.E., Mordacq, C., Morelle, G., Mouly, S.J., Muñoz-Barrera, A., Nafati, C., Nagashima, S., Nakagama, Y., Neven, B., Neves, J.F., Ng, L.F., Ng, Y.Y., Nielly, H., Medina, Y.N., Cuadros, E.N., Ocejo-Vinyals, J.G., Okamoto, K., Oualha, M., Ouedrani, A., Özçelik, T., Ozkaya-Parlakay, A., Pagani, M., Pan-Hammarström, Q., Papadaki, M., Parizot, C., Parola, P., Pascreau, T., Paul, S., Paz-Artal, E., Pedraza, S., González Pellecer, N.C., Pellegrini, S., de Diego, R.P., Pérez-Fernández, X.L., Philippe, A., Philippot, Q., Picod, A., de Chambrun, M.P., Piralla, A., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Poulakou, G., Pouletty, M.S., Pourshahnazari, P., Qiu-Chen, J.L., Quentric, P., Rambaud, T., Raoult, D., Raoult, V., Rebillat, A.S., Redin, C., Resmini, L., Ricart, P., Richard, J.C., Rigo-Bonnin, R., Rivet, N., Rivière, J.G., Rocamora-Blanch, G., Rodero, M.P., Rodrigo, C., Rodriguez, L.A., Rodriguez-Gallego, C., Rodriguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Roux, D., Rovina, N., Rozenberg, F., Ruch, Y., Ruiz, M., Ruiz Del Prado, M.Y., Ruiz-Rodriguez, J.C., Sabater-Riera, J., Saks, K., Salagianni, M., Sanchez, O., Sánchez-Montalvá, A., Sánchez-Ramón, S., Schidlowski, L., Schluter, A., Schmidt, J., Schmidt, M., Schuetz, C., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L., Seminario, A.G., Sene, D., Seng, P., Senoglu, S., Seppänen, M., Llovich, A.S., Shahrooei, M., Shcherbina, A., Siguret, V., Siouti, E., Smadja, D.M., Smith, N., Sobh, A., Solanich, X., Solé-Violán, J., Soler, C., Soler-Palacín, P., Sözeri, B., Stella, G.M., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiotte, Y., Taupin, J.L., Tavernier, S.J., Tello, L.V., Terrier, B., Thiery, G., Thorball, C., Thorn, K., Thumerelle, C., Tipu, I., Tolstrup, M., Tomasoni, G., Toubiana, J., Alvarez, J.T., Triantafyllia, V., Trouillet-Assant, S., Troya, J., Tsang, OTY, Tserel, L., Tso, EYK, Tucci, A., Tüter Öz, Ş.K., Ursini, M.V., Utsumi, T., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., Van Den Rym, A.M., Vandernoot, I., Velez-Santamaria, V., Zuniga Veliz, S.P., Vidigal, M.C., Viel, S., Vilain, C., Vilaire-Meunier, M.E., Villar-García, J., Vincent, A., Vogt, G., Voiriot, G., Volokha, A., Vuotto, F., Wauters, E., Wauters, J., Wu, AKL, Wu, T.C., Yahşi, A., Yesilbas, O., Yildiz, M., Young, B.E., Yükselmiş, U., Zatz, M., Zecca, M., Zuccaro, V., Jens, V.P., Lambrecht, B.N., Eva, V.B., Cédric, B., Levi, H., Eric, H., Bauters, F., De Clercq, J., Cathérine, H., Hans, S., Leslie, N., Florkin, B., Boulanger, C., Vanderlinden, D., Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Danielson, J.J., Dobbs, K., Kashyap, A., Ding, L., Dalgard, C.L., Sottini, A., Quaresima, V., Quiros-Roldan, E., Rossi, C., Bettini, L.R., D'Angio', M., Beretta, I., Montagna, D., Licari, A., Marseglia, G.L., Batten, I., Reddy, C., McElheron, M., Noonan, C., Connolly, E., Fallon, A., Storgaard, M., Jørgensen, S., Erikstrup, C., Pedersen, O.B., Sørensen, E., Mikkelsen, S., Dinh, K.M., Larsen, MAH, Paulsen, I.W., Von Stemann, J.H., Hansen, M.B., Ostrowski, S.R., Townsend, L., Cheallaigh, C.N., Bergin, C., Martin-Loeches, I., Dunne, J., Conlon, N., Bourke, N., O'Farrelly, C., Abel, L., Allavena, C., Andrejak, C., Angoulvant, F., Azoulay, C., Bachelet, D., Bartoli, M., Basmaci, R., Behilill, S., Beluze, M., Benech, N., Benkerrou, D., Bhavsar, K., Bitker, L., Bouadma, L., Bouscambert-Duchamp, M., Paz, P.C., Cervantes-Gonzalez, M., Chair, A., Chirouze, C., Coelho, A., Cordel, H., Couffignal, C., Couffin-Cadiergues, S., d'Ortenzio, E., De Montmollin, E., Debard, A., Debray, M.P., Deplanque, D., Descamps, D., Desvallée, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Duval, X., Eloy, P., Enouf, V., Epaulard, O., Esperou, H., Esposito-Farese, M., Etienne, M., Garot, D., Gault, N., Gaymard, A., Ghosn, J., Gigante, T., Gilg, M., Goehringer, F., Guedj, J., Hoctin, A., Hoffmann, I., Houas, I., Hulot, J.S., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Kerroumi, Y., Khalil, A., Khan, C., Kimmoun, A., Laine, F., Laouénan, C., Laribi, S., Le, M., Le Bris, C., Le Gac, S., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lemaignen, A., Lemee, V., Lescure, F.X., Letrou, S., Levy, Y., Lina, B., Lingas, G., Lucet, J.C., Machado, M., Malvy, D., Mambert, M., Manuel, A., Mentré, F., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Nguyen, D., Noret, M., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Peigne, V., Petrov-Sanchez, V., Peytavin, G., Pham, H., Picone, O., Piquard, V., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Rossignol, P., Roy, C., Schneider, M., Su, R., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Tual, C., Tubiana, S., Van Der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Annereau, J.P., Briseño-Roa, L., Gribouval, O., Pelet, A., Alcover, A., Aschard, H., Bousso, P., Brodin, P., Bruhns, P., Cerf-Bensussan, N., Cumano, A., D'Enfert, C., Deriano, L., Dillies, M.A., Di Santo, J., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hedestam, G.K., Hercberg, S., Ingersoll, M.A., Lantz, O., Kenny, R.A., Ménager, M., Michel, F., Patin, E., Rausell, A., Rieux-Laucat, F., Rogge, L., Fontes, M., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Zimmer, C., Albert, M.L., Duffy, D., Quintana-Murci, L., Alavoine, L., Behillil, S., Burdet, C., Charpentier, C., Dechanet, A., Ecobichon, J.L., Frezouls, W., Houhou, N., Lehacaut, J., Manchon, P., Nouroudine, M., Quintin, C., Thy, M., van der Werf, S., Vignali, V., Chahine, A., Waucquier, N., Migaud, M.C., Djossou, F., Mergeay-Fabre, M., Lucarelli, A., Demar, M., Bruneau, L., Gérardin, P., Maillot, A., Payet, C., Laviolle, B., Paris, C., Desille-Dugast, M., Fouchard, J., Pistone, T., Perreau, P., Gissot, V., Le Goas, C., Montagne, S., Richard, L., Bouiller, K., Desmarets, M., Meunier, A., Lefévre, B., Jeulin, H., Legrand, K., Lomazzi, S., Tardy, B., Gagneux-Brunon, A., Bertholon, F., Botelho-Nevers, E., Kouakam, C., Leturque, N., Roufai, L., Amat, K., Espérou, H., Hendou, S., van Agtmael, M., Algera, A.G., Appelman, B., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bonta, P., Bos, L., Botta, M., de Brabander, J., de Bree, G., de Bruin, S., Buis, DTP, Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Dijkstra, M., Dongelmans, D.A., Dujardin, RWG, Elbers, P., Fleuren, L., Geijtenbeek, SGT, Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., Lim, EHT, van Mourik, N., Nellen, J., Nossent, E.J., Paulus, F., Peters, E., Pina-Fuentes, DAI, van der Poll, T., Preckel, 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Hans-Heinrich [0000-0003-0554-0244], Eto, Shohei [0000-0002-2885-7490], García-Prat, Marina [0000-0001-5387-1908], Bizien, Lucy [0000-0001-9163-9122], Parra-Martínez, Alba [0000-0002-9564-8912], Dorgham, Karim [0000-0001-9539-3203], Alkhater, Suzan [0000-0001-7315-6581], Rigo-Bonnin, Raúl [0000-0001-5511-074X], Roussel, Lucie [0000-0001-5355-702X], Vinh, Donald C. [0000-0003-1347-7767], Ostrowski, Sisse Rye [0000-0001-5288-3851], Condino-Neto, Antonio [0000-0002-1069-3117], Prando, Carolina [0000-0002-9570-9770], Spaan, András N. [0000-0001-5981-7259], Gilardin, Laurent [0000-0001-9212-0859], Yang, Rui [0000-0003-4427-2158], Fellay, Jacques [0000-0002-8240-939X], Bilguvar, Kaya [0000-0002-7313-7652], Mane, Shrikant M. [0000-0002-3267-5139], Anderson, MarK S. [0000-0002-3093-4758], Boisson, Bertrand [0000-0001-5240-3555], Béziat, Vivien [0000-0002-4020-824X], Andreakos, Evangelos [0000-0001-5536-1661], Hermine, Olivier [0000-0003-2574-3874], Pujol, Aurora [0000-0002-9606-0600], Peterson, Pärt [0000-0001-6755-791X], Haljasmägi, Liis [0000-0001-7162-9808], Mogensen, Trine [0000-0002-1853-9704], Lamballerie, Xavier de [0000-0001-7895-2720], Zins, Marie [0000-0002-4540-4282], Soler-Palacín, Pere [0000-0002-0346-5570], Colobran, Roger [0000-0002-5964-536X], Gorochov, Guy [0000-0003-2097-9677], Solanich, Xavier [0000-0002-2572-2187], Susen, Sophie [0000-0001-5953-163X], Martínez-Picado, Javier [0000-0002-4916-2129], Gregersen, Peter K. [0000-0003-1613-1518], Migaud, Mélanie [0000-0003-3062-1214], Piemonti, Lorenzo [0000-0002-2172-2198], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Notarangelo, Luigi D. [0000-0002-8335-0262], Su, Helen C. [0000-0002-5582-9110], Kisand, Kai [0000-0002-5426-4648], Okada, Satoshi [0000-0002-4622-5657], Puel, Anne [0000-0003-2603-0323], Jouanguy, Emmanuelle [0000-0002-7358-9157], Tiberghien, Pierre [0000-0002-9310-8322], Zhang, Qian [0000-0002-9040-3289], Särekannu, Karita [0000-0002-5984-668X], Cobat, Aurélie [0000-0001-7209-6257], Abel, Laurent [0000-0001-7016-6493], Casanova, Jean-Laurent [0000-0002-7782-4169], Prost, Nicolas de [0000-0002-4833-4320], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Luyt, Charles-Edouard [0000-0001-7424-2705], Amador-Borrero, Blanco [0000-0001-6170-8721], Poissy, Julien [0000-0001-6017-5353], Richard, Pascale [0000-0003-1864-3824], Cognasse, Fabrice [0000-0001-8041-928X], Troya, Jesús [0000-0001-7323-114X], Trouillet-Assant, Sophie [0000-0001-6439-4705], Belot, Alexandre [0000-0003-4902-5332], Saker, Kahina [0000-0001-8825-5400], Rivière, Jacques G. [0000-0003-1055-2063], Gentile, Stephanie [0000-0003-3858-9503], Rosen, Lindsey B. [0000-0001-5894-3878], Shaw, Elana [0000-0001-9265-8026], Dalmau, David [0000-0003-1936-478X], Tharaux, Pierre-Louis [0000-0002-6062-5905], Stépanian, Alain [0000-0002-2942-0901], Mégarbane, Bruno [0000-0002-2522-2764], Triantafyllia, Vasiliki [0000-0001-5832-4014], Fekkar, Arnaud [0000-0001-9954-075X], Heath, James R. [0000-0001-5356-4385], Franco, José Luis [0000-0001-5664-6415], Anaya, Juan Manuel [0000-0002-6444-1249], Imberti, Luisa[0000-0002-2075-8391], Bonfanti, Paolo [0000-0001-7289-8823], Castagnoli, Riccardo [0000-0003-0029-9383], Snow, Andrew L. [0000-0002-8728-6691], Holland, Steven M. [0000-0003-3207-5464], Biggs, Catherine M. [0000-0002-4363-2660], Moncada-Velez, Marcela [0000-0002-3073-5345], Arias, Andrés Augusto [0000-0002-9478-8403], Lorenzo, Lazaro [0000-0001-6648-8684], Boucherit, Soraya [0000-0002-8819-7594], Anglicheau, Dany [0000-0001-5793-6174], Planas, Anna M. [0000-0002-6147-1880], Haerynck, Filomeen [0000-0001-9161-7361], Duvlis, Sotirija [0000-0001-8587-7386], Nussbaum, Robert [0000-0003-3445-8880], Bousfiha, Ahmed Aziz [0000-0002-5011-9873], El Bakkouri, Jalila [0000-0003-2303-3369], Ramírez-Santana, Carolina [0000-0003-2137-4899], Paul, Stephanie [0000-0002-8830-4273], Pan-Hammarström, Qiang [0000-0003-1990-8804], Hammarström, Lennart [0000-0002-8635-9609], Dupont, Annabelle [0000-0002-1554-9931], Kurolap, Alina [0000-0002-7005-3621], Metz, Christine N. [0000-0002-1013-1691], Aiuti, Alessandro [0000-0002-5398-1717], Casari, Giorgio [0000-0002-0115-8980], Lampasona, Vito [0000-0001-5162-8445], Ciceri, Fabio [0000-0003-0873-0123], Barreiros, Lucila [0000-0002-9818-2345], Domínguez-Garrido, Elena [0000-0002-2066-0511], Vidigal, Mateus [0000-0002-8895-652X], Zatz, Mayana [0000-0003-3970-8025], Beek, Diederik van der [0000-0002-4571-044X], Stepanovskyy, Yuriy [0000-0001-6339-5490], Boyarchuk, Oksana [0000-0002-1234-0040], Nukui, Yoko [0000-0002-6123-5212], Vidaur, Loreto [0000-0002-6720-4900], Tangye, Stuart G. [0000-0002-5360-5180], Burrel, Sonia [0000-0002-7783-2601], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Klocperk, Adam [0000-0002-1526-4557], Kan, Nelli [0000-0003-3564-6496], Shcherbina, Anna [0000-0002-3113-4939], Lau, Yu-Lung [0000-0002-4780-0289], Leung, Daniel [0000-0002-9360-6233], Coulongeat, Matthieu [0000-0003-1986-3546], Marlet, Julien [0000-0002-8645-8703], Koning, Rutger [0000-0003-3128-5072], Reyes, Luis Felipe [0000-0003-1172-6539], Venet, Fabienne [0000-0003-0462-4235], Monneret, Guillaume [0000-0002-9961-5739], Nussenzweig, Michel C. [0000-0003-0592-8564], Baris, Hagit N. [0000-0003-4065-7560], Hagin, David [0000-0003-2702-1031], Wauters, Joost [0000-0002-5983-3897], Meyts, Isabelle [0000-0003-1214-0302], Dyer, Adam [0000-0003-1356-510X], Bourke, Nollaig [0000-0003-4313-6859], Halwani, Rabih [0000-0002-6516-7771], and Sharif-Askari, Narjes Saheb [0000-0003-0482-6777]

Subjects
Interferon Type I/immunology, AUTOIMMUNITY, [SDV]Life Sciences [q-bio], Interferó, Gastroenterology, COVID-19 (Malaltia), Immunoglobulin G, Basic medicine, 0302 clinical medicine, Medicine and Health Sciences, 80 and over, Immunologia, Young adult, Child, Neutralizing, MYASTHENIA-GRAVIS PATIENTS, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, education.field_of_study, biology, General Medicine, Middle Aged, 3. Good health, COVID-19/immunology, Settore MED/03, 030220 oncology & carcinogenesis, Child, Preschool, Interferon Type I, Antibody, medicine.symptom, INTERFERON, Adult, medicine.medical_specialty, Adolescent, Critical Illness, Immunology, Population, Aged, Antibodies, Neutralizing, Autoantibodies, COVID-19, Case-Control Studies, Humans, Infant, Infant, Newborn, Interferon-alpha, Young Adult, Alpha interferon, Immunoglobulins, IMMUNITY, Asymptomatic, PATIENT, 03 medical and health sciences, Internal medicine, medicine, Preschool, education, Antibodies, Neutralizing/blood, HOMENS, 030304 developmental biology, ANTINUCLEAR, business.industry, Autoantibody, Case-control study, Antibodies, Neutralizing/immunology, Autoantibodies/blood, Autoantibodies/immunology, COVID-19/mortality, Immunoglobulin G/blood, Immunoglobulin G/immunology, Interferon-alpha/immunology, Newborn, DISTINCT FUNCTIONS, ALPHA, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Immunoglobulines
Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 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 1124 deceased patients (aged 20 days to 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 individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-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 individuals 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., 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), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Awards (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, 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 GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, 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). P.B., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the NIAID and NIDCR, NIH (grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (reference ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (AJF202019), Dubai, UAE, and a COVID-19 research grant (CoV19-0307) from the University of Sharjah, UAE. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a UNSW Sydney COVID Rapid Response Initiative Grant. L.I. reported funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). L.I. and G. L. Marseglia reported funding from Regione Lombardia, Italy (project Risposta immune in pazienti con COVID-19 e co-morbidità). This research was partially supported by the Instituto de Salud Carlos III (COV20/0968). J.R.H. reported funding from Biomedical Advanced Research and Development Authority HHSO10201600031C. S.O. reports funding Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (grant number JP20fk0108531). G.G. was supported by ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The Three-City (3C) Study was conducted under a partnership agreement among the INSERM, the Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques”. S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under contract no. 75N91019D00024, task order no. 75N91021F00001. J.W. is supported by an FWO Fundamental Clinical Mandate (1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF). C.R.-G. and colleagues of the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017 and OA20/024), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). C.M.B. is supported by a MSFHR Health Professional-Investigator Award. P.Q.H. and L.H. were funded by the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX (806-2018) and Colciencias contract 713-2016 (code 111574455633)]. A.K. was in part supported by grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies; by the KU Leuven C1 grant C16/18/007; by a VIB-GC PID grant; by the FWO frants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). M.Vi received funding from the São Paulo Research Foundation (FAPESP) (grant number 2020/09702-1) and JBS SA (grant number 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation

Published
2021
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29. Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency

Author

Lévy, Romain, Gothe, Florian, Momenilandi, Mana, Magg, Thomas, Materna, Marie, Peters, Philipp, Raedler, Johannes, Philippot, Quentin, Rack-Hoch, Anita, Langlais, David, Bourgey, Mathieu, Lanz, Anna-Lisa, Ogishi, Masato, Rosain, Jérémie, Martin, Emmanuel, Latour, Sylvain, Vladikine, Natasha, Distefano, Marco, Khan, Taushif, Rapaport, Franck, Schulz, Marian, Holzer, Ursula, Fasth, Anders, Sogkas, Georgios, Speckmann, Carsten, Troilo, Arianna, Bigley, Venetia, Roppelt, Anna, Dinur-Schejter, Yael, Toker, Ori, Bronken Martinsen, Karen, Sherkat, Roya, Somekh, Ido, Somech, Raz, Shouval, Dror, Kühl, Jörn-Sven, Ip, Winnie, Mcdermott, Elizabeth, Cliffe, Lucy, Ozen, Ahmet, Baris, Safa, Rangarajan, Hemalatha, Jouanguy, Emmanuelle, Puel, Anne, Bustamante, Jacinta, Alyanakian, Marie-Alexandra, Fusaro, Mathieu, Wang, Yi, Kong, Xiao-Fei, Cobat, Aurélie, Boutboul, David, Castelle, Martin, Aguilar, Claire, Hermine, Olivier, Cheminant, Morgane, Suarez, Felipe, Yildiran, Alisan, Bousfiha, Aziz, Al-Mousa, Hamoud, Alsohime, Fahad, Cagdas, Deniz, Abraham, Roshini, Knutsen, Alan, Fevang, Borre, Bhattad, Sagar, Kiykim, Ayca, Erman, Baran, Arikoglu, Tugba, Unal, Ekrem, Kumar, Ashish, Geier, Christoph, Baumann, Ulrich, Neven, Bénédicte, Calas, Julie, Feuille, Elizabeth, Chan, Angela, Yesil, Gozde, Nammour, Justine, Bandet, Élise, Picard, Capucine, Benhsaien, Ibtihal, Lang, Peter, Atschekzei, Faranaz, Warnatz, Klaus, Hambleton, Sophie, Desai, Mukesh, Karakoc-Aydiner, Elif, Kolukisa, Burcu, Al-Muhsen, Saleh, Alosaimi, Mohammed, Cipe, Funda, Alazami, Anas, Hancioglu, Gonca, Can Meydan, Bilge, Sorte, Hanne, Stray-Pedersen, Asbjørg, Mammayil, Geetha, Tökmeci, Nazan, Shcherbina, Anna, Stepensky, Polina, Nasereddin, Adeeb, Rouzaud, Claire, Hoshino, Akihiro, Shamriz, Oded, Ledder, Oren, Maccari, Maria, Castro, Carla, Grimbacher, Bodo, Schmidt, Reinhold, Collin, Matthew, Zakharova, Victorya, Rohlfs, Meino, Walz, Christoph, Abel, Laurent, Malissen, Bernard, Marr, Nico, Klein, Christoph, Casanova, Jean-Laurent, Hauck, Fabian, Béziat, Vivien, Lévy R., Gothe F., Momenilandi M., Magg T., Materna M., Peters P., Raedler J., Philippot Q., Rack-Hoch A. L., Langlais D., et al., Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunophénomique (CIPHE), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), and ANR-21-CE15-0034,CARMIL2,Bases moléculaires, cellulaires et immunologiques de la déficience combinée résultant de mutations dans CARMIL2(2021)

Subjects
CD4-Positive T-Lymphocytes, Phenotype, CD28 Antigens, [SDV]Life Sciences [q-bio], Microfilament Proteins, Mutation, Immunology, Humans, Immunology and Allergy
Abstract

International audience; Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4 + and CD8 + memory T cells and CD4 + T REG s. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV + smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4 + T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.

Published
2022
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30. Decoding the Human Genetic and Immunological Basis of COVID-19 mRNA Vaccine-Induced Myocarditis

Author

Bolze, Alexandre, Mogensen, Trine H., Zhang, Shen-Ying, Abel, Laurent, Andreakos, Evangelos, Arkin, Lisa M., Borghesi, Alessandro, Brodin, Petter, Hagin, David, Novelli, Giuseppe, Okada, Satoshi, Peter, Jonny, Renia, Laurent, Severe, Karine, Tiberghien, Pierre, Vinh, Donald C., Aiuti, Alessandro, Al-Muhsen, Saleh, Al-Mulla, Fahd, Amara, Ali, Anderson, Mark S., Arias, Andrés A., Feldman, Hagit Baris, Bastard, Paul, Belot, Alexandre, Biggs, Catherine M., Bogunovic, Dusan, Bousfiha, Ahmed A., Butte, Manish J., Christodoulou, John, Cobat, Aurelie, Colobran, Roger, Condino-Neto, Antonio, Constantinescu, Stefan N., Dalgard, Clifton L., Duval, Xavier, Eloy, Philippine, Espinosa-Padilla, Sara, Fellay, Jacques, Flores, Carlos, Franco, José Luis, Froidure, Antoine, Gorochov, Guy, Gregersen, Peter K., Haerynck, Filomeen, Halwani, Rabih, Hammarström, Lennart, Itan, Yuval, Jouanguy, Emmanuelle, Karamitros, Timokratis, Lau, Yu-Lung, Mansouri, Davood, Mentre, France, Meyts, Isabelle, Mironska, Kristina, Morio, Tomohiro, Ng, Lisa F. P., Novelli, Antonio, O’Farrelly, Cliona, Okamoto, Keisuke, Ozcelik, Tayfun, Pan-Hammarström, Qiang, de Diego, Rebeca Perez, Perez-Tur, Jordi, Perlin, David S., Pesole, Graziano, Planas, Anna M., Prando, Carolina, Pujol, Aurora, Quintana-Murci, Lluis, Resnick, Igor, Rodríguez-Gallego, Carlos, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänen, Mikko R. J., Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Soler-Palacín, Pere, Soumelis, Vassili, Spaan, András N., Tancevski, Ivan, Tangye, Stuart G., Tayoun, Ahmad Abou, Temel, Şehime G. lsün, Thorball, Christian, Trouillet-Assant, Sophie, Turvey, Stuart E., Uddin, K. MFurkan, van de Beek, Diederik, von Bernuth, Horst, Zhang, Qian, Cirulli, Elizabeth T., Casanova, Jean-Laurent, Hsieh, Elena W. Y., Neurology, AII - Infectious diseases, and ANS - Neuroinfection & -inflammation

Subjects
Myocarditis, COVID-19 Vaccines, Settore MED/03, Vaccination, Immunology, Humans, COVID-19, Immunology and Allergy, Human Genetics, IMUNOGENICIDADE DA VACINA
Abstract

More than 10 billion doses of COVID-19 vaccines have been administered worldwide in the span of 18 months, providing an unprecedented opportunity to study and understand immunological responses and clinical reactions to vaccines. While severe adverse reactions to live-attenuated viral or bacterial vaccines have been successfully deciphered since the 1950s, with the discovery of a wide range of underlying inborn errors of immunity [1, 2], there is currently no molecular, cellular, and immunological explanation for life-threatening reactions to any other type of vaccine. COVID-19 mRNA vaccines are very effective at preventing hypoxemic COVID-19 pneumonia. For example, their efficacy for preventing invasive mechanical ventilation and in-hospital death has been estimated at 90% (95% CI = 88–91%) [3]. COVID-19 mRNA vaccines are also well tolerated by most people, with either no side effects or mild local/systemic reactions, such as pain at the injection site, fever, or chills in the days following vaccination [4]. However, rare but serious adverse events have been observed, including anaphylaxis, myocarditis, Guillain-Barré syndrome, transverse myelitis, Bell’s palsy, and multisystem inflammatory syndrome [4,5,6,7]. These adverse events have a combined prevalence of about 90 per million doses administered [4]. It is unknown whether they are triggered by the adjuvant (lipid nanoparticles for the mRNA vaccines), the vaccine antigen (the perfusion-stabilized spike protein translated by the human cells), the core components of the vaccine (the nucleoside-modified mRNA), or a combination thereof. Some possible mechanisms have been suggested [8,9,10], but the underlying immunopathology and, hence, the risk factors predisposing a minority of vaccinees to experience any of these severe reactions remain unknown.

Published
2022

31. Invasive Pneumococcal Disease in Children Can Reveal a Primary Immunodeficiency

Author

Gaschignard, Jean, Levy, Corinne, Chrabieh, Maya, Boisson, Bertrand, Bost-Bru, Cécile, Dauger, Stéphane, Dubos, François, Durand, Philippe, Gaudelus, Joël, Gendrel, Dominique, Le Guen, Christèle Gras, Grimprel, Emmanuel, Guyon, Gaël, Jeudy, Catherine, Jeziorski, Eric, Leclerc, Francis, Léger, Pierre-Louis, Lesage, Fabrice, Lorrot, Mathie, Pellier, Isabelle, Pinquier, Didier, de Pontual, Loïc, Sachs, Philippe, Thomas, Caroline, Tissières, Pierre, Valla, Frédéric V., Desprez, Philippe, Frémeaux-Bacchi, Véronique, Varon, Emmanuelle, Bossuyt, Xavier, Cohen, Robert, Abel, Laurent, Casanova, Jean-Laurent, Puel, Anne, and Picard, Capucine

Published
2014
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32. 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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33. Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia

Author

Zhang, Qian, Matuozzo, Daniela, Le Pen, Jérémie, Lee, Danyel, Moens, Leen, Asano, Takaki, Bohlen, Jonathan, Liu, Zhiyong, Moncada-Velez, Marcela, Kendir-Demirkol, Yasemin, Jing, Huie, Bizien, Lucy, Marchal, Astrid, Abolhassani, Hassan, Delafontaine, Selket, Bucciol, Giorgia, COVID Human Genetic Effort, Bayhan, Gulsum Ical, Keles, Sevgi, Kiykim, Ayca, Hancerli, Selda, Haerynck, Filomeen, Florkin, Benoit, Hatipoglu, Nevin, Ozcelik, Tayfun, Morelle, Guillaume, Zatz, Mayana, Ng, Lisa F P, Lye, David Chien, Young, Barnaby Edward, Leo, Yee-Sin, Dalgard, Clifton L, Lifton, Richard P, Renia, Laurent, Meyts, Isabelle, Jouanguy, Emmanuelle, Hammarström, Lennart, Pan-Hammarström, Qiang, Boisson, Bertrand, Bastard, Paul, Su, Helen C, Boisson-Dupuis, Stéphanie, Abel, Laurent, Rice, Charles M, Zhang, Shen-Ying, Cobat, Aurélie, Casanova, Jean-Laurent, Froidure, Antoine, School of Biological Sciences, Lee Kong Chian School of Medicine (LKCMedicine), A*STAR Infectious Diseases Labs, National Centre for Infectious Diseases, National University of Singapore, Tan Tock Seng Hospital, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, and Özçelik, Tayfun

Subjects
Adult, SARS-CoV-2, Immunology, Inheritance Patterns, COVID-19, Pneumonia, COVID-19/genetics, Simplex-Virus Encephalitis, Settore MED/03, Interferon Type I, Pyogenic Bacterial-Infections, Medicine and Health Sciences, Immunology and Allergy, Humans, Medicine [Science], Child
Abstract

Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (

Published
2022

34. Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Author

Bastard, Paul, Vazquez, Sara, Liu, Jamin, Laurie, Matthew, Wang, Chung, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Zamecnik, Colin, Philippot, Quentin, Rosain, Jérémie, Catherinot, Emilie, Willmore, Andrew, Mitchell, Anthea, Bair, Rebecca, Garçon, Pierre, Kenney, Heather, Fekkar, Arnaud, Salagianni, Maria, Poulakou, Garyphallia, Siouti, Eleni, Sahanic, Sabina, Tancevski, Ivan, Weiss, Günter, Nagl, Laurenz, Manry, Jérémy, Duvlis, Sotirija, Arroyo-Sánchez, Daniel, Paz Artal, Estela, Rubio, Luis, Perani, Cristiano, Bezzi, Michela, Sottini, Alessandra, Quaresima, Virginia, Roussel, Lucie, Vinh, Donald, Reyes, Luis, Garzaro, Margaux, Hatipoglu, Nevin, Boutboul, David, Tandjaoui-Lambiotte, Yacine, Borghesi, Alessandro, Aliberti, Anna, Cassaniti, Irene, Venet, Fabienne, Monneret, Guillaume, Halwani, Rabih, Sharif-Askari, Narjes, Danielson, Jeffrey, Burrel, Sonia, Morbieu, Caroline, Stepanovskyy, Yurii, Bondarenko, Anastasia, Volokha, Alla, Boyarchuk, Oksana, Gagro, Alenka, Neuville, Mathilde, Neven, Bénédicte, Keles, Sevgi, Hernu, Romain, Bal, Antonin, Novelli, Antonio, Novelli, Giuseppe, Saker, Kahina, Ailioaie, Oana, Antolí, Arnau, Jeziorski, Eric, Rocamora-Blanch, Gemma, Teixeira, Carla, Delaunay, Clarisse, Lhuillier, Marine, Le Turnier, Paul, Zhang, Yu, Mahevas, Matthieu, Pan-Hammarström, Qiang, Abolhassani, Hassan, Bompoil, Thierry, Dorgham, Karim, Gorochov, Guy, Laouenan, Cédric, Rodríguez-Gallego, Carlos, Ng, Lisa, Renia, Laurent, Pujol, Aurora, Belot, Alexandre, Raffi, François, Allende, Luis, Martinez-Picado, Javier, Ozcelik, Tayfun, Imberti, Luisa, Notarangelo, Luigi, Troya, Jesus, Solanich, Xavier, Zhang, Shen-Ying, Puel, Anne, Wilson, Michael, Trouillet-Assant, Sophie, Abel, Laurent, Jouanguy, Emmanuelle, Ye, Chun, Cobat, Aurélie, Thompson, Leslie, Andreakos, Evangelos, Zhang, Qian, Anderson, Mark, Casanova, Jean-Laurent, Derisi, Joseph, Achille, Cristian, Aiuti, Alessandro, Al-Muhsen, Saleh, Al-Mulla, Fahd, Angelini, Micol, Arias, Andrés, Aytekin, Gokhan, Baldanti, Fausto, Feldman, Hagit, Bergami, Federica, Biggs, Catherine, Bogunovic, Dusan, Bolze, Alexandre, Bondarenko, Anastasiia, Bousfiha, Ahmed, Brodin, Petter, Bryceson, Yenan, Bustamante, Carlos, Butte, Manish, Casari, Giorgio, Christodoulou, John, Condino-Neto, Antonio, Constantinescu, Stefan, Conti, Francesca, Cooper, Megan, Dalgard, Clifton, Desai, Murkesh, Drolet, Beth, El Baghdadi, Jamila, Ergun, Recai, Ergun, Dilek, Espinosa-Padilla, Sara, Fellay, Jacques, Flores, Carlos, Franco, José, Froidure, Antoine, Ghirardello, Stefano, Gregersen, Peter, Grimbacher, Bodo, Haerynck, Filomeen, Hagin, David, Hammarström, Lennart, Heath, James, Henrickson, Sarah, Hsieh, Elena, Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich, Kanat, Fikret, Karamitros, Timokratis, Kisand, Kai, Kopcha, Vasyl, Korda, Mykhaylo, Ku, Cheng-Lung, Lau, Yu-Lung, Ling, Yun, Lucas, Carrie, Maniatis, Tom, Mansouri, Davood, Maródi, László, Meyts, Isabelle, Milner, Joshua, Mironska, Kristina, Mogensen, Trine, Mojoli, Francesco, Morandeira, Francisco, Morio, Tomohiro, O'Farrelly, Cliona, Okada, Satoshi, Okamoto, Keisuke, Pagani, Michele, Pape, Jean, de Diego, Rebeca, Perlin, David, Pesole, Graziano, Pession, Andrea, Piralla, Antonio, Planas, Anna, Prando, Carolina, Quintana-Murci, Lluis, Ramaswamy, Sathishkumar, Resnick, Igor, Rigo-Bonnin, Raúl, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänen, Mikko, Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Snow, Andrew, Soler-Palacín, Pere, Spaan, András, Tangye, Stuart, Abou Tayoun, Ahmad, Tulek, Baykal, Turvey, Stuart, Uddin, K, Uddin, Mohammed, Clément, Bénédicte, Abe-Jones, Yumiko, Asthana, Saurabh, Bhide, Sharvari, Calfee, Carolyn, Carrillo, Sidney, Chak, Suzanna, Collins, Zachary, Erle, David, Fragiadakis, Gabriela, Ghale, Rajani, Hendrickson, Carolyn, Jauregui, Alejandra, Kangelaris, Kirsten, Krummel, Matthew, Langelier, Charles, Lea, Tasha, Lee, Deanna, Leligdowicz, Aleksandra, Leroux, Carolyn, Lota, Raphael, Matthay, Michael, Nguyen, Viet, Patel, Ravi, Pierce, Logan, Prasad, Priya, Rao, Arjun, Rashid, Ahmad, Rodriguez, Nicklaus, Samad, Bushra, Shaw, Cole, Sigman, Austin, Tang, Kevin, Altamirano, Luz, Ward, Alyssa, Woodruff, Prescott, Allavena, Clotilde, Andrejak, Claire, Angoulvant, François, Azoulay, Cecile, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behilill, Sylvie, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bhavsar, Krishna, Bitker, Laurent, Bouadma, Lila, Bouscambert, Maude, Paz, Pauline, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, D’ortenzio, Eric, de Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diehl, Jean-Luc, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Duval, Xavier, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lemaignen, Adrien, Lemee, Véronique, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean, Machado, Moïse, Malvy, Denis, Mambert, Marina, Manuel, Aldric, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Peigne, Vincent, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Poissy, Julien, Puéchal, Oriane, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Tubiana, Sarah, van der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for the Study of Primary Immunodeficiencies [Paris], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], Grand Hôpital de l'Est Francilien (GHEF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 4th Department of Internal Medicine, ATTIKON University General Hospital, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute, Goce Delchev University (UGD), Génétique Evolutive Humaine - Human Evolutionary Genetics, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Basic medicine, Settore MED/03, [SDV]Life Sciences [q-bio], Immunology, COVID-19, Pneumònia, Pneumonia, General Medicine
Abstract

International audience; Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.

Published
2022
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35. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

Author

Andreakos, Evangelos, Abel, Laurent, Vinh, Donald C., Kaja, Elżbieta, Drolet, Beth A., Zhang, Qian, O’Farrelly, Cliona, Novelli, Giuseppe, Rodríguez-Gallego, Carlos, Haerynck, Filomeen, Prando, Carolina, Pujol, Aurora, Bastard, Paul, Biggs, Catherine M., Bigio, Benedetta, Boisson, Bertrand, Bolze, Alexandre, Bondarenko, Anastasiia, Brodin, Petter, Chakravorty, Samya, Christodoulou, John, Cobat, Aurelié, Condino-Neto, Antonio, Constantinescu, Stefan N., Feldman, Hagit Baris, Fellay, Jacques, Flores, Carlos, Halwani, Rabih, Jouanguy, Emmanuelle, Lau, Yu-Lung, Meyts, Isabelle, Mogensen, Trine H., Okada, Satoshi, Okamoto, Keisuke, Ozcelik, Tayfun, Pan-Hammarström, Qiang, Diego, Rebeca Pérez de, Planas, Anna M., Puel, Anne, Quintana-Murci, Lluis, Renia, Laurent, Resnick, Igor, Sediva, Anna, Shcherbina, Anna, Slaby, Ondrej, Tancevski, Ivan, Turvey, Stuart E., Uddin, K. M. Furkan, van de Beek, Diederik, Zatz, Mayana, Zawadzki, Pawel, Zhang, Shen-Ying, Su, Helen C., Casanova, Jean-Laurent, Spaan, András N., Biomedical Research Foundation of the Academy of Athens (BRFAA), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Human genetics of infectious diseases: Complex predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], University of Wisconsin-Madison, Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Trinity College Dublin, University of Rome Tor Vergata, Hospital Universitario de Gran Canaria Dr Negrin, Universidad de las Palmas de Gran Canaria (ULPGC), Ghent University Hospital, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Institució Catalana de Recerca i Estudis Avançats (ICREA), CIBER de Enfermedades Raras (CIBERER), University of British Columbia (UBC), Karolinska Institutet [Stockholm], Emory University [Atlanta, GA], University of Melbourne, Universidade de São Paulo = University of São Paulo (USP), Université Catholique de Louvain = Catholic University of Louvain (UCL), Tel Aviv University (TAU), School of Life Sciences [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), University of Sharjah (UoS), Department of Paediatrics and Adolescent Medicine [HKU], The University of Hong Kong (HKU), University Hospitals Leuven [Leuven], Department of Microbiology, Immunology and Transplantation [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Aarhus University Hospital, Hiroshima University, Tokyo Medical and Dental University [Japan] (TMDU), Bilkent University [Ankara], Department of Biosciences and Nutrition [Karolinska Insitutet, Sueden] (BioNut), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Agency for science, technology and research [Singapore] (A*STAR), Nanyang Technological University [Singapour], Faculty of Medicine [Brno] (MED / MUNI), Masaryk University [Brno] (MUNI), Leopold Franzens Universität Innsbruck - University of Innsbruck, University of Amsterdam [Amsterdam] (UvA), Adam Mickiewicz University in Poznań (UAM), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), University Medical Center [Utrecht], The Laboratory of Human Genetics of Infectious Diseases is supported by the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, 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 Fisher Center for Alzheimer’s Research Foundation, the Meyer 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-COV05, the Fondation du Souffle, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. E.A. is supported by research grants from the European Commission’s Horizon 2020 research and innovation program (IMMUNAID, grant no. 779295, CURE, grant no. 767015 and TO_AITION grant no. 848146) and the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). C.O.F. is supported in part by the Science Foundation Ireland COVID-19 Program. G.N. is supported by a grant awarded to Regione Lazio (Research Group Projects 2020) no. A0375-2020-36663, GecoBiomark. A.P. is supported in part by the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342) and the CERCA Program/Generalitat de Catalunya. H.S. is supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. A.S. is supported in part by the European Union’s Horizon 2020 research and innovation program (Marie Sklodowska-Curie grant no. 789645)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), Özçelik, Tayfun, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Université Paris Cité, Equipe HAL, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), National Human Genome Research Institute (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, Université de Paris, European Commission, Hellenic Foundation for Research and Innovation, Science Foundation Ireland, Regione Lazio, Generalitat de Catalunya, and National Institute of Allergy and Infectious Diseases (US)

Subjects
Tuberculosis, autoantibodies, Immunology, Plasmodium vivax, restriction, Disease, Asymptomatic, Risk Assessment, Chemokine receptor, Genetic Heterogeneity, Immunity, Risk Factors, il28b, medicine, Immunology and Allergy, Animals, Humans, PLASMODIUM, Genetic Predisposition to Disease, Disease Resistance, Genetics, biology, Transmission (medicine), SARS-CoV-2, transmission, Autoantibody, COVID-19, virus diseases, deficiency, Protective Factors, hiv-1 infection, biology.organism_classification, medicine.disease, immunity, Phenotype, tuberculosis, Settore MED/03, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Viral infection, Host-Pathogen Interactions, Perspective, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, Infection, individuals, inborn-errors
Abstract

SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection., The Laboratory of Human Genetics of Infectious Diseases is supported by the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, 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 Fisher Center for Alzheimer’s Research Foundation, the Meyer 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-COV05, the Fondation du Souffle, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. E.A. is supported by research grants from the European Commission’s Horizon 2020 research and innovation program (IMMUNAID, grant no. 779295, CURE, grant no. 767015 and TO_AITION grant no. 848146) and the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). C.O.F. is supported in part by the Science Foundation Ireland COVID-19 Program. G.N. is supported by a grant awarded to Regione Lazio (Research Group Projects 2020) no. A0375-2020-36663, GecoBiomark. A.P. is supported in part by the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342) and the CERCA Program/Generalitat de Catalunya. H.S. is supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. A.S. is supported in part by the European Union’s Horizon 2020 research and innovation program (Marie Sklodowska-Curie grant no. 789645).

Published
2022
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36. Autoantibodies against type I interferons are associated with multi-organ failure in COVID-19 patients

Author

Koning, Rutger, Bastard, Paul, Casanova, Jean-Laurent, Brouwer, Matthijs C, van de Beek, Diederik, Study group members AMC, Wiersinga, W. Joost, de Bree, Godelieve J., Geerlings, Suzanne E., Goorhuis, Bram, Grobusch, Martin P., Harris, Vanessa C., Hermans, Sabine M., Hovius, Joppe W. R., Nellen, Jeanine, van der Poll, Tom, Prins, Jan M., Stijnis, Cornelis S., van der Valk, Marc, van Vugt, Michele, Hollmann, Markus W., Preckel, Prof. dr. , Benedikt, Veelo, Denise P., Intensive care medicine, Neurology, Graduate School, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, and ACS - Microcirculation

Subjects
2019-20 coronavirus outbreak, Letter, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Autoantibody, Medicine, Critical Care and Intensive Care Medicine, business, Multi organ, Interferon type I, medicine.drug
Published
2021
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37. TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C

Author

MIS-C Clinicians, Hoste, Levi, Roels, Lisa, Naesens, Leslie, Bosteels, Victor, Vanhee, Stijn, Dupont, Sam, Bosteels, Cedric, Browaeys, Robin, Vandamme, Niels, Verstaen, Kevin, Roels, Jana, Van Damme, Karel F A, Maes, Bastiaan, De Leeuw, Elisabeth, Declercq, Jozefien, Aegerter, Helena, Seys, Leen, Smole, Ursula, De Prijck, Sofie, Vanheerswynghels, Manon, Claes, Karlien, Debacker, Veronique, Van Isterdael, Gert, Backers, Lynn, Claes, Kathleen B M, Bastard, Paul, Jouanguy, Emmanuelle, Zhang, Shen-Ying, Mets, Gilles, Dehoorne, Joke, Vandekerckhove, Kristof, Schelstraete, Petra, Willems, Jef, Stordeur, Patrick, Janssens, Sophie, Beyaert, Rudi, Saeys, Yvan, Casanova, Jean-Laurent, Lambrecht, Bart N, Haerynck, Filomeen, Tavernier, Simon J, Daelemans, Siel, Pulmonary Medicine, Clinical sciences, Growth and Development, and Pediatrics

Subjects
Male, T-Lymphocytes, CHILDREN, LIPOPOLYSACCHARIDE, infectious diseases, Lymphocyte Activation, HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, DISEASE, pediatric SARS-CoV-2 infection, Monocytes, Cohort Studies, IFNγ signature, TIM3+ TRBV11-2 T cells, Medicine and Health Sciences, Immunology and Allergy, immunodysregulation syndrome, Child, Complement Activation, Hepatitis A Virus Cellular Receptor 2, Interleukin-15, B-Lymphocytes, Superantigens, Patrolling, hemic and immune systems, Systemic Inflammatory Response Syndrome, Cell biology, Killer Cells, Natural, Interferon Type I, SHOCK, Cytokines, Female, Adolescent, MULTISYSTEM INFLAMMATORY SYNDROME, Immunology, Receptors, Antigen, T-Cell, CD16+ NK cells, MIS-C, SARS-COV-2, CD16, Biology, Article, Infectious Disease and Host Defense, Interferon-gamma, Humans, Pediatrics, Perinatology, and Child Health, Cell Proliferation, Inflammation, INTERFERON-GAMMA, SARS-CoV-2, Receptors, IgG, Biology and Life Sciences, COVID-19, Immunity, Humoral, Enterocytes, patrolling monocytes, BARRIER FUNCTION, Alveolar Epithelial Cells, Blood Vessels, Signature (topology)
Abstract

MIS-C is a novel immunodysregulation syndrome in children with a history of SARS-CoV-2 infection. This study employs a multi-omics approach to explore its immunopathogenesis. The authors show that IFNγ-mediated interactions between T cells, monocytes, and NK cells reside at the heart of the disease., In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis., Graphical Abstract

Published
2021
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38. Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans

Author

O’neill, Mary, Quach, Hélène, Pothlichet, Julien, Aquino, Yann, Bisiaux, Aurélie, Zidane, Nora, Deschamps, Matthieu, Libri, Valentina, Hasan, Milena, Zhang, Shen-Ying, Zhang, Qian, Matuozzo, Daniela, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, Naffakh, Nadia, Rotival, Maxime, Quintana-Murci, Lluis, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Éco-Anthropologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Diaccurate SAS, Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Rockefeller University [New York], Howard Hughes Medical Institute (HHMI), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus, Collège de France (CdF (institution)), This work was supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10- LABX-62-IBEID) and 'Milieu Intérieur' (ANR-10-LABX-69-01), the Fondation de France (n°00106080), and the Fondation pour la Recherche Médicale (Equipe FRM DEQ20180339214). MO’N was supported by a European Molecular Biology Organization long-term fellowship (ALTF 229-2017)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Éco-Anthropologie (EA), Collège Doctoral, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus (CNRS-UMR3569), Collège de France - Chaire Génomique humaine et évolution, European Project: ALTF 229-2017, Gestionnaire, Hal Sorbonne Université, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, and European Molecular Biology Organization long-term fellowship - ALTF 229-2017 - INCOMING

Subjects
Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, population, Black People, GPI-Linked Proteins, Monocytes, influenza virus, White People, transcriptomics, Young Adult, Hypothesis and Theory, Influenza, Human, Immunology and Allergy, Humans, Sequence Analysis, RNA, ancestry, Receptors, IgG, Middle Aged, single-cell ‘omics, Influenza A virus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, single-cell 'omics, Single-Cell Analysis, Ribosomes
Abstract

International audience; There is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use single-cell RNA-sequencing to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. We show widespread inter-individual variability in the percentage of IAV-infected monocytes. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such as IFITM3 , MX1 and OAS3 . Upon IAV challenge, we find that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. We also uncover a stronger resistance of CD16 + monocytes to IAV infection, together with CD16 + -specific mRNA expression of IL6 and TNF in response to IAV. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number of CD16 + monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Based on these data, we hypothesize that higher basal monocyte activation, driven by environmental factors and/or weak-effect genetic variants, underlies the lower cellular susceptibility to IAV infection of individuals of African ancestry relative to those of European ancestry. Further studies are now required to investigate how such cellular differences in IAV susceptibility translate into population differences in clinical outcomes and susceptibility to severe influenza.

Published
2021
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39. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Author

Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J., Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G., Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G., Arias, Andres Augusto, Morelle, Guillaume, Kyheng, Christèle, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M., Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E., Pérez de Diego, Rebeca, Keles, Sevgi, Aytekin, Gokhan, Metin Akcan, Ozge, Bryceson, Yenan T., Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C. I. Edvard, Norlin, Anna-Carin, Campbell, Tessa M., Covill, Laura E., Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N., Dalgard, Clifton L., Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P., Bastard, Paul, Notarangelo, Luigi D., Abel, Laurent, Su, Helen C., Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Al-Muhsen, Saleh, Al-Mulla, Fahd, Anderson, Mark S., Andreakos, Evangelos, Arias, Andrés A., Feldman, Hagit Baris, Belot, Alexandre, Biggs, Catherine M., Bogunovic, Dusan, Bondarenko, Anastasiia, Bousfiha, Ahmed A., Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Condino-Neto, Antonio, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Fellay, Jacques, Franco, José Luis, Froidure, Antoine, Gregersen, Peter K., Haerynck, Filomeen, Hagin, David, Halwani, Rabih, Heath, James R., Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Kisand, Kai, Ku, Cheng-Lung, Lau, Yu-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Meyts, Isabelle, Milner, Joshua D., Mironska, Kristina, Mogensen, Trine H., Morio, Tomohiro, Ng, Lisa F.P., O'Farrelly, Cliona, Okada, Satoshi, de Diego, Rebeca Perez, Planas, Anna M., Prando, Carolina, Quintana-Murci, Lluis, Renia, Laurent, Resnick, Igor, Rodríguez-Gallego, Carlos, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänen, Mikko R.J., Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Tancevski, Ivan, Tangye, Stuart G., Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., van de Beek, Diederik, Vinh, Donald C., von Bernuth, Horst, Zatz, Mayana, Zawadzki, Pawel, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, AlKhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Arrestier, Romain, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Boyarchuk, Oksana, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Dalmau, David, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gilardin, Laurent, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Klocperk, Adam, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lagier, Jean-Christophe, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, LAU, Yu-Lung, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Leung, Daniel, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Bolanos Lima, Edson Jose Adrian, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Luyt, Charles-Edouard, Lye, David C, Magnone, Cinthia, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Martinez-Picado, Javier, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morandeira, Francisco, Morange, Pierre-Emmanuel, Mordacq, Cléemence, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paul, Stéphane, Paz-Artal, Estela, Pedraza, Sigifredo, González Pellecer, Nancy Carolina, Pellegrini, Silvia, de Diego, Rebeca Pérez, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Ploin, Dominique, Poissy, Julien, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie S, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Didier, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rigo-Bonnin, Raúl, Rivet, Nadia, Rivière, Jacques G, Rocamora-Blanch, Gemma, Rodero, Mathieu P, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Seijo, Luis, Seminario, Analia Gisela, Sene, Damien, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Solanich, Xavier, Solé-Violán, Jordi, Soler, Catherine, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, Thorn, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Triantafyllia, Vasiliki, Trouillet-Assant, Sophie, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wauters, Joost, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Pelet, Anna, Andrejak, Claire, Angoulvant, François, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behilill, Sylvie, Beluze, Marine, Benkerrou, Dehbia, Bhavsar, Krishna, Bouadma, Lila, Bouchez, Sabelline, Bouscambert, Maude, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Couffignal, Camille, Couffin-Cadiergues, Sandrine, d’Ortenzio, Eric, Debray, Marie-Pierre, Deconinck, Lauren, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Duval, Xavier, Elharrar, Brigitte, Eloy, Philippine, Enouf, Vincent, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Devouge, Eglantine Ferrand, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Khalil, Antoine, Khan, Coralie, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Malvy, Denis, Mambert, Marina, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Nseir, Saad, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Perpoint, Thomas, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rabaud, Christian, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Van Der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Alavoine, Loubna, Behillil, Sylvie, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, van der Werf, Sylvie, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Laine, Fabrice, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefévre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David T.P., Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul, Fleuren, Lucas, Geerlings, Suzanne, Geijtenbeek, Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Koning, Rutger, Lim, Endry H.T., van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan A.I., van der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits C.F.J., Schinkel, Michiel, Schultz, Marcus J., Schrauwen, Femke A.P., Schuurmans, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos), Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Tompkins, Miranda F., Alba, Camille, Hupalo, Daniel N., Rosenberger, John, Sukumar, Gauthaman, Wilkerson, Matthew D., Zhang, Xijun, Lack, Justin, Oler, Andrew J., Dobbs, Kerry, Delmonte, Ottavia M., Danielson, Jeffrey J., Bettini, Laura Rachele, D’Angio, Mariella, Beretta, Ilaria, Imberti, Luisa, Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Neurology, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rockefeller University [New York], Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Helix [San Mateo, CA], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Özçelik, Tayfun, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pathology, Asano, T., Boisson, B., Onodi, F., Matuozzo, D., Moncada-Velez, M., Renkilaraj, M. R. L. M., Zhang, P., Meertens, L., Bolze, A., Materna, M., Korniotis, S., Gervais, A., Talouarn, E., Bigio, B., Seeleuthner, Y., Bilguvar, K., Zhang, Y., Neehus, A. -L., Ogishi, M., Pelham, S. J., Le Voyer, T., Rosain, J., Philippot, Q., Soler-Palacin, P., Colobran, R., Martin-Nalda, A., Riviere, J. G., Tandjaoui-Lambiotte, Y., Chaibi, K., Shahrooei, M., Darazam, I. A., Olyaei, N. A., Mansouri, D., Hatipoglu, N., Palabiyik, F., Ozcelik, T., Novelli, G., Novelli, A., Casari, G., Aiuti, A., Carrera, P., Bondesan, S., Barzaghi, F., Rovere-Querini, P., Tresoldi, C., Franco, J. L., Rojas, J., Reyes, L. F., Bustos, I. G., Arias, A. A., Morelle, G., Kyheng, C., Troya, J., Planas-Serra, L., Schluter, A., Gut, M., Pujol, A., Allende, L. M., Rodriguez-Gallego, C., Flores, C., Cabrera-Marante, O., Pleguezuelo, D. E., Diego, R. P. D., Keles, S., Aytekin, G., Akcan, O. M., Bryceson, Y. T., Bergman, P., Brodin, P., Smole, D., Smith, C. I. E., Norlin, A. -C., Campbell, T. M., Covill, L. E., Hammarstrom, L., Pan-Hammarstrom, Q., Abolhassani, H., Mane, S., Marr, N., Ata, M., Ali, F. A., Khan, T., Spaan, A. N., Dalgard, C. L., Bonfanti, P., Biondi, A., Tubiana, S., Burdet, C., Nussbaum, R., Kahn-Kirby, A., Snow, A. L., Bustamante, J., Puel, A., Boisson-Dupuis, S., Zhang, S. -Y., Beziat, V., Lifton, R. P., Bastard, P., Notarangelo, L. D., Abel, L., Su, H. C., Jouanguy, E., Amara, A., Soumelis, V., Cobat, A., Zhang, Q., Casanova, J. -L., Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University, the St. Giles Foundation, the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at the 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 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) and 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, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) 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, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1, AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by 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 FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX, 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045). A.-L.N. was supported by the Bettencourt Schueller Foundation and the International PhD program of the Imagine Institute. P. Bergman and C.I.E.S received support from the Center for Medical Innovation (CIMED), the Swedish Medical Research Council and the Stockholm County Council (ALF-project). Part of this work was generated within the European Reference Network for rare primary immunodeficiency, autoinflammatory and autoimmune diseases (RITA)., Members of French COVID Cohort Study Group: Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Marie Bartoli5, Romain Basmaci6, Sylvie Behilill7, Marine Beluze8, Dehbia Benkerrou9, Krishna Bhavsar4, Lila Bouadma4, Sabelline Bouchez10, Maude Bouscambert11, Minerva Cervantes-Gonzalez4, Anissa Chair4, Catherine Chirouze12, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric d’Ortenzio5, Marie-Pierre Debray4, Lauren Deconinck4, Dominique Deplanque15, Diane Descamps4, Mathilde Desvallée16, Alpha Diallo5, Alphonsine Diouf13, Céline Dorival9, François Dubos17, Xavier Duval4, Brigitte Elharrar18, Philippine Eloy4, Vincent Enouf7, Hélène Esperou14, Marina Esposito-Farese4, Manuel Etienne19, Eglantine Ferrand Devouge19, Nathalie Gault4, Alexandre Gaymard11, Jade Ghosn4, Tristan Gigante20, Morgane Gilg20, Jérémie Guedj21, Alexandre Hoctin13, Isabelle Hoffmann4, Ikram Houas14, Jean-Sébastien Hulot22, Salma Jaafoura14, Ouifiya Kafif4, Florentia Kaguelidou23, Sabrina Kali4, Antoine Khalil4, Coralie Khan16, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre5, Hervé Le Nagard24, François-Xavier Lescure4, Sophie Letrou4, Yves Levy25, Bruno Lina11, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy26, Marina Mambert13, France Mentré4, Amina Meziane9, Hugo Mouquet7, Jimmy Mullaert4, Nadège Neant24, Duc Nguyen26, Marion Noret27, Saad Nseir17, Aurélie Papadopoulos14, Christelle Paul5, Nathan Peiffer-Smadja4, Thomas Perpoint28, Ventzislava Petrov-Sanchez5, Gilles Peytavin4, Huong Pham4, Olivier Picone6, Valentine Piquard4, Oriane Puéchal29, Christian Rabaud30, Manuel Rosa-Calatrava11, Bénédicte Rossignol20, Patrick Rossignol30, Carine Roy4, Marion Schneider4, Richa Su4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé9, Olivier Terrier11, Jean-François Timsit4, Christelle Tual31, Sarah Tubiana4, Sylvie Van Der Werf7, Noémie Vanel32, Aurélie Veislinger31, Benoit Visseaux4, Aurélie Wiedemann25, Yazdan Yazdanpanah4, ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), 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), Asano, T, Boisson, B, Onodi, F, Matuozzo, D, Moncada-Velez, M, Maglorius Renkilaraj, M, Zhang, P, Meertens, L, Bolze, A, Materna, M, Korniotis, S, Gervais, A, Talouarn, E, Bigio, B, Seeleuthner, Y, Bilguvar, K, Zhang, Y, Neehus, A, Ogishi, M, Pelham, S, Le Voyer, T, Rosain, J, Philippot, Q, Soler-Palacín, P, Colobran, R, Martin-Nalda, A, Rivière, J, Tandjaoui-Lambiotte, Y, Chaïbi, K, Shahrooei, M, Darazam, I, Olyaei, N, Mansouri, D, Hatipoğlu, N, Palabiyik, F, Ozcelik, T, Novelli, G, Novelli, A, Casari, G, Aiuti, A, Carrera, P, Bondesan, S, Barzaghi, F, Rovere-Querini, P, Tresoldi, C, Franco, J, Rojas, J, Reyes, L, Bustos, I, Arias, A, Morelle, G, Christèle, K, Troya, J, Planas-Serra, L, Schlüter, A, Gut, M, Pujol, A, Allende, L, Rodriguez-Gallego, C, Flores, C, Cabrera-Marante, O, Pleguezuelo, D, de Diego, R, Keles, S, Aytekin, G, Akcan, O, Bryceson, Y, Bergman, P, Brodin, P, Smole, D, Smith, C, Norlin, A, Campbell, T, Covill, L, Hammarström, L, Pan-Hammarström, Q, Abolhassani, H, Mane, S, Marr, N, Ata, M, Al Ali, F, Khan, T, Spaan, A, Dalgard, C, Bonfanti, P, Biondi, A, Tubiana, S, Burdet, C, Nussbaum, R, Kahn-Kirby, A, Snow, A, Bustamante, J, Puel, A, Boisson-Dupuis, S, Zhang, S, Béziat, V, Lifton, R, Bastard, P, Notarangelo, L, Abel, L, Su, H, Jouanguy, E, Amara, A, Soumelis, V, Cobat, A, Zhang, Q, and Casanova, J

Subjects
Male, SUBSETS, [SDV]Life Sciences [q-bio], Penetrance, REDUNDANT, COVID-19 (Malaltia), 0302 clinical medicine, Resposta immunitària, 80 and over, Medicine and Health Sciences, Medicine, Young adult, Child, X-linked recessive inheritance, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, education.field_of_study, PYOGENIC BACTERIAL-INFECTIONS, virus diseases, Genetic Diseases, X-Linked, HUMANS, General Medicine, Middle Aged, PROTECTIVE IMMUNITY, 3. Good health, Pedigree, Settore MED/03, Immune System Diseases, Genetic Diseases, Child, Preschool, Cohort, medicine.symptom, SINGLE-STRANDED RNA, Adult, Adolescent, Aged, Alleles, COVID-19, Humans, Infant, Toll-Like Receptor 7, Young Adult, Immunology, Population, Asymptomatic, Article, 03 medical and health sciences, HOST-DEFENSE, Immune response, Allele, Preschool, education, 030304 developmental biology, TOLL-LIKE RECEPTORS, business.industry, RECOGNITION, Proteins, X-Linked, medicine.disease, Pneumonia, 3121 General medicine, internal medicine and other clinical medicine, PLASMACYTOID DENDRITIC CELLS, business, Proteïnes, 030215 immunology
Abstract

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract. Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University; the St. Giles Foundation; the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS); NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at the 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 Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01) and 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, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects; the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics). The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by 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 FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX; 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045)

Published
2021
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40. X-linked recessive TLR7 deficiency in similar to 1% of men under 60 years old with life-threatening COVID-19

Author

Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Renkilaraj, Majistor Raj Luxman Maglorius, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J, Le Voyer, Tom, Rosain, Jeremie, Philippot, Quentin, Soler-Palacin, Pere, Colobran, Roger, Martin-Nalda, Andrea, Riviere, Jacques G, Tandjaoui-Lambiotte, Yacine, Chaibi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G, Arias, Andres Augusto, Morelle, Guillaume, Kyheng, Christele, Troya, Jesus, Planas-Serra, Laura, Schluter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M, Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E, de Diego, Rebeca Perez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, Bryceson, Yenan T, Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, CI Edvard, Norlin, Anna-Carin, Campbell, Tessa M, Covill, Laura E, Hammarstrom, Lennart, Pan-Hammarstrom, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, Andras N, Dalgard, Clifton L, Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L, Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stephanie, Zhang, Shen-Ying, Beziat, Vivien, Lifton, Richard P, Bastard, Paul, Notarangelo, Luigi D, Abel, Laurent, Su, Helen C, Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurelie, Zhang, Qian, Casanova, Jean-Laurent, and Gunst, Jan

Subjects
TOLL-LIKE RECEPTORS, PYOGENIC BACTERIAL-INFECTIONS, Science & Technology, SUBSETS, Immunology, RECOGNITION, virus diseases, HUMANS, REDUNDANT, PROTECTIVE IMMUNITY, HOST-DEFENSE, PLASMACYTOID DENDRITIC CELLS, Life Sciences & Biomedicine, SINGLE-STRANDED RNA
Abstract

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract. ispartof: SCIENCE IMMUNOLOGY vol:6 issue:62 ispartof: location:United States status: published

Published
2021

41. Single-cell epitope and RNA-sequencing reveals the systemic immune associations with type I interferon autoantibodies in COVID-19

Author

van der Wijst, Monique G.P., Vazquez, Sara E., Hartoularos, George C., Bastard, Paul, Grant, Tianna, Bueno, Raymund, Lee, David S., Greenland, John R., Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Mann, Sabrina A., Lynch, Kara L., Yun, Cassandra, Havlir, Diane V., Chamie, Gabriel, Marquez, Carina, Greenhouse, Bryan, Lionakis, Michail S., Norris, Philip J., Dumont, Larry J., Kelly, Kathleen, Zhang, Peng, Zhang, Qian, Gervais, Adrian, Le Voyer, Tom, Whatley, Alexander, Si, Yichen, Byrne, Ashley, Combes, Alexis J., Rao, Arjun Arkal, Song, Yun S., Fragiadakis, Gabriela K., Kangelaris, Kirsten, Calfee, Carolyn S., Erle, David J., Hendrickson, Carolyn, Krummel, Matthew F., Woodruff, Prescott G., Langelier, Charles R., Casanova, Jean-Laurent, Derisi, Joseph L., Anderson, Mark S., and Ye, Chun Jimmie

Subjects
Single-cell, FOS: Clinical medicine, Immunology, Interferon, RNA-seq, Viral Infections, COVID, Autoantibodies
Abstract

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN-specific autoantibodies in peripheral blood samples from 19% of patients with critical cases and 6% of patients with severe cases. We found no type I IFN autoantibodies in individuals with moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non-COVID-19 controls revealed a lack of type I IFN-stimulated gene (ISG-I) responses in myeloid cells from patients with critical cases. This was especially evident in dendritic cell populations isolated from critical cases producing type I IFN-specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) on the surface of monocytes isolated from patients with critical cases early in the disease course. LAIR-1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN-specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms., Type I interferon autoantibodies in COVID-19 are associated with deficient interferon response and elevated LAIR-1 expression in peripheral leukocytes.

Published
2021
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42. SARS-CoV-2-related MIS-C:A key to the viral and genetic causes of Kawasaki disease?

Author

Sancho-Shimizu, Vanessa, Brodin, Petter, Cobat, Aurélie, Biggs, Catherine M., Toubiana, Julie, Lucas, Carrie L., Henrickson, Sarah E., Belot, Alexandre, Haddad, Elie, Beland, Kathie, Pujol, Aurora, Schlüter, Agatha, Planas-Serra, Laura, Aguilera-Albesa, Sergio, Valencia-Ramos, Juan, Rodríguez-Palmero, Agustí, Gut, Marta, Rivière, Jacques G., Colobran, Roger, Soler-Palacin, Pere, Rodriguez-Gallego, Carlos, Perez De Diego, Rebeca, Flores, Carlos, Alsina, Laia, Blazquez-Gamero, Daniel, Jordan, Iolanda, Keles, Sevgi, Emiroglu, Melike, Akcan, Ozge Metin, Alkan, Gulsum, Aytekin, Selma Erol, Gul, Yahya, Tüter Öz, Şadiye Kübra, Bozdemir, Sefika Elmas, Bayhan, Gulsum Iclal, Yüksek, Saliha Kanık, Parlakay, Aslınur Özkaya, Gülhan, Belgin, Yahşi, Aysun, Kilic, Ahmet Osman, Karbuz, Adem, Erdeniz, Emine Hafize, Özkan, Esra Akyüz, Orbak, Zerrin, Aydemir, Şehnaz, Celik, Jale Bengi, Kandemir, Bahar, Aytekin, Gökhan, Kapakli, Hasan, Yarar, Volkan, Yosunkaya, Alper, Vatansev, Hulya, Aytekin, Caner, Torun, Selda Hancerli, Nepesov, Serdar, Coskuner, Taner, Sözeri, Betül, Demirkol, Yasemin Kendir, Kasapcopur, Ozgur, Yıldız, Mehmet, Sevketoglu, Esra, Hatipoğlu, Nevin, Özçelik, Tayfun, Yesilbas, Osman, Gayretli Aydin, Zeynep Gökçe, Sediva, Anna, Klocperk, Adam, Bloomfield, Marketa, Meyts, Isabelle, Delafontaine, Selket, Haerynck, Filomeen, Hoste, Levi, Shahrooei, Mohammad, Marque, Laura, Neves, João Farela, Novelli, Giuseppe, Novelli, Antonio, Aiuti, Alessandro, Casari, Giorgio, Bousfiha, Amed Aziz, Almuhsen, Saleh Zaid, Sobh, Ali, Gagro, Alenka, Bajolle, Fanny, Bonnet, Damien, Lebon, Pierre, Lei, Weite, Lee, Danyel, Seeleuthner, Yoann, Zhang, Peng, Maglorius, Majistor, Philippot, Quentin, Pelham, Simon, Bastard, Paul, Zhang, Qian, Jouanguy, Emmanuelle, Puel, Anne, Herberg, Jethro, Kuijpers, Taco W, Bellos, Evangelos, Kaforou, Myrsini, Menikou, Stephanie, Pan-Hammarström, Qiang, Hammarström, Lennart, Abolhassani, Hassan, Bryceson, Yenan, Condino-Neto, Antonio, Prando, Carolina, Bando, Silvia Yumi, Cavalcanti, Andre, Fellay, Jacques, Blanchard-Hohner, Giradine, Mansouri, Davood, Mahmoudi, Shima, Boyarchuk, Oksana, Volokha, Alla, Bondarenko, Anastasiia, Stepanovskiy, Yuriy, Mogensen, Trine, van de Beek, Diederik, Andreakos, Evangelos, Papadaki, Maria, Abou Tayoun, Ahmad, Halwani, Rabih, Al-Mulla, Fahd, Franco, José Luis, Lau, Yu-Lung, Kwan, Mike, Imai, Kohsuke, Okada, Satoshi, Bolze, Alexandre, Butte, Manish J., Hsieh, Elena, Drolet, Beth A, Arkin, Lisa, Itan, Yuval, Maniatis, Tom, Arditi, Moshe, Cooper, Megan, Schmitt, Erica, Chakravorty, Samya, Anderson, Mark S., Su, Helen C., Notarangelo, Luigi D., MIS-C@CHGE, [missing], Tangye, Stuart G., Milner, Joshua D., Levin, Michael, Abel, Laurent, Bogunovic, Dusan, Casanova, Jean-Laurent, Zhang, Shen-Ying, Human genetics of infectious diseases: Complex predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP), 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), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Funded by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (R01AI088364 to J.-L. Casanova and S.-Y. Zhang, R01AI148963, R01AI151029, and R01AI150300 to D. Bogunovic, K08AI135091 to S.E. Henrickson, R21AI144315-02S1 to C.L. Lucas), the National Center for Advancing Translational Sciences, National Institutes of Health Clinical and Translational Science Award program (UL1 TR001866), the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (UM1HG006504 and U24HG008956), Institut National de la Santé et de la Recherche Médicale and Université de Paris, the French National Research Agency (ANR) Résilience-Covid-19 grant GenMIS-C, the ANR '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 ANR project AABIFNCOV (ANR-20-CO11-0001), the French Foundation for Medical Research (EQU201903007798), the French Foundation for Medical Research and ANR GENCOVID project, the ANRSCOV05 project, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, UK Research and Innovation Future Leader’s Fellowship (MR/S032304/1), the NIHR Imperial Biomedical Research Centre at Imperial College Healthcare NHS Trust (70931), the Burroughs Wellcome Fund Career Awards for Medical Scientists, the Clinical Immunology Society, the American Academy of Allergy Asthma and Immunology, the Michael Smith Foundation for Health Research, the National Health and Medical Research Council of Australia, and the University of New South Wales Sydney COVID Rapid Response Initiative (to S.G. Tangye)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), 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), Imperial College BRC, Imperial College Healthcare NHS Trust- BRC Funding, and UKRI Future Leader's Fellowship

Subjects
0301 basic medicine, viruses, Systemic Inflammatory Response Syndrome/epidemiology, Genome-wide association study, CHILDREN, COVID-19 (Malaltia), Pathogenesis, 0302 clinical medicine, hemic and lymphatic diseases, INFECTION, Medicine and Health Sciences, Immunology and Allergy, 030212 general & internal medicine, skin and connective tissue diseases, Child, 11 Medical and Health Sciences, COVID-19/epidemiology, Pediatria, Malaltia de Kawasaki, Systemic Inflammatory Response Syndrome, Settore MED/03, Inflammation Mediators/blood, Perspective, Cytokines, SHOCK, medicine.symptom, Inflammation Mediators, Lymphohistiocytosis, Hemophagocytic/genetics, congenital, hereditary, and neonatal diseases and abnormalities, HUMAN CORONAVIRUS NL63, SUSCEPTIBILITY LOCI, MULTISYSTEM INFLAMMATORY SYNDROME, Inflammation/etiology, Immunology, Innate Immunity and Inflammation, Inflammation, Biology, Mucocutaneous Lymph Node Syndrome, Cytokines/blood, Models, Biological, Lymphohistiocytosis, Hemophagocytic, SARS-CoV-2/immunology, 03 medical and health sciences, Immune system, Immunity, CORONARY ANEURYSMS, medicine, otorhinolaryngologic diseases, Immunodeficiency, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Pandemics, SARS-CoV-2, Mucocutaneous Lymph Node Syndrome/epidemiology, COVID-19, biochemical phenomena, metabolism, and nutrition, medicine.disease, Systemic inflammatory response syndrome, 030104 developmental biology, Etiology, Kawasaki disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, PIMS-TS, Biomarkers, Human Disease Genetics, Genètica, Biomarkers/blood, Genome-Wide Association Study
Abstract

SARS-CoV-2 is the trigger of MIS-C, which suggests that other viruses may trigger different forms of Kawasaki disease. The discovery of inborn errors of immunity underlying MIS-C would facilitate that of inborn errors of immunity to viruses underlying Kawasaki disease., Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.

Published
2021
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43. 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

44. Human TANK-binding kinase 1 is required for early autophagy induction upon herpes simplex virus 1 infection

Author

Ahmad, Liyana, Mashbat, Bayarchimeg, Leung, Corwin, Brookes, Charlotte, Hamad, Samar, Krokowski, Sina, Shenoy, Avinash R, Lorenzo, Lazaro, Levin, Michael, O'Hare, Peter, Zhang, Shen-Ying, Casanova, Jean-Laurent, Mostowy, Serge, Sancho-Shimizu, Vanessa, Medical Research Foundation, and Medical Research Council (MRC)

Subjects
ACTIVATION, Science & Technology, Allergy, ENCEPHALITIS, TBK1, 1107 Immunology, Immunology, Life Sciences & Biomedicine
Published
2018

45. Under the influence.

Subjects
*INFLUENZA, *RESPIRATORY distress syndrome, *ANTIVIRAL agents, *INTERFERONS, *GENETIC disorders, *IMMUNOLOGY
Abstract

The article focuses on a paper published by researchers Jean-Laurent Casanova in the periodical "Science" on the possibility that influenza is a genetic disease. Topics include the use of gene sequencing in researching the severity of influenza on patients, the presence of the protein interferon regulatory factor 7, and the development of acute respiratory distress syndrome.

Published
2015

46. Mendelian Susceptibility to Mycobacterial Diseases (MSMD) in Colombian Patients

Author

Fernández Echeverri Diana, González Loaiza Daniel, Moncada-Vélez Marcela, Orrego Julio Cesar, Rojas Jessica Lineth, Arango Franco Carlos, Gonzalez Natalia, Pérez Vélez Carlos Mario, Sierra Juan Esteban, Wilches Alejandra, Arango Catalina, Restrepo Andrea, Trujillo Mónica, Garcés Carlos, Isaza-Correa Johana Marcela, Gongora Diego, Casanova Jean-Laurent, Arias Andres, Bustamante Jacinta, and Franco Jose

Subjects
Immunology, Immunology and Allergy
Published
2015
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50. Prevalence and risk factors for latent tuberculosis infection among healthcare workers in Morocco.

Author

Sabri, Ayoub, Quistrebert, Jocelyn, Naji Amrani, Hicham, Abid, Ahmed, Zegmout, Adil, Abderrhamani Ghorfi, Ismail, Souhi, Hicham, Boucaid, Abdelhalim, Benali, Anas, Abilkassem, Rachid, Kmari, Mohamed, Hassani, Amal, Lahcen, Belyamani, Siah, Samir, Schurr, Erwin, Boisson-Dupuis, Stéphanie, Casanova, Jean-Laurent, Lahlou, Amine, Laatiris, Abdelkader, and Louzi, Lhoussain

Subjects
DISEASE risk factors, BCG vaccines, TUBERCULIN test, AGE groups, DISEASE prevalence, TUBERCULOSIS
Abstract

Increased prevalence of latent tuberculosis infection (LTBI) has been observed among high-risk populations such as healthcare workers (HCWs). The results may depend on the method of LTBI assessment, interferon-gamma release assay (IGRA) and/or tuberculin skin test (TST). Here, we investigated the prevalence and risk factors for LTBI assessed by both IGRAs and TST in HCWs living in Morocco, a country with intermediate tuberculosis (TB) endemicity and high BCG vaccination coverage. HCWs were recruited in two Moroccan hospitals, Rabat and Meknes. All the participants underwent testing for LTBI by both IGRA (QuantiFERON-TB Gold In-Tube, QFT-GIT) and TST. Different combinations of IGRA and TST results defined the LTBI status. Risk factors associated with LTBI were investigated using a mixed-effect logistic regression model. The prevalence of LTBI among 631 HCWs (age range 18–60 years) varied from 40.7% (95%CI 36.9–44.5%) with QFT-GIT to 52% (95%CI 48.2–56.0%) with TST using a 10 mm cut-off. The highest agreement between QFT-GIT and TST (κ = 0.50; 95%CI 0.43–0.56) was observed with the 10 mm cut-off for a positive TST. For a definition of LTBI status using a double positive result for both QFT-GIT and TST, significant associations were found with the following risk factors: being male (OR = 2.21; 95%CI 1.40–3.49; p = 0.0007), belonging to age groups 35–44 years (OR = 2.43; 95%CI 1.45–4.06; p = 0.0007) and even more 45–60 years (OR = 4.81; 95%CI 2.72–8.52; p = 7.10−8), having a family history of TB (OR = 6.62; 95%CI 2.59–16.94; p = 8.10−5), and working at a pulmonology unit (OR = 3.64; 95%CI 1.44–9.23; p = 0.006). Smoking was associated with LTBI status when defined by a positive QFT-GIT result (OR = 1.89; 95%CI 1.12–3.21; p = 0.02). A high prevalence of LTBI was observed among HCWs in two Moroccan hospitals. Male gender, increased age, family history of TB, and working at a pulmonology unit were consistent risk factors associated with LTBI. [ABSTRACT FROM AUTHOR]

Published
2019
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