المؤلفون: Casanova, Jean-Laurent, Puel, Anne, Zhang, Qian, Cobat, Aurélie, Soumelis, Vassili, Amara, Ali, Jouanguy, Emmanuelle, Su, Helen C, Abel, Laurent, Notarangelo, Luigi D, Bastard, Paul, Lifton, Richard P, Béziat, Vivien, Zhang, Shen-Ying, Boisson-Dupuis, Stéphanie, 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, HatipoÄŸlu, 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, Christèle, Kyheng, 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, de Diego, Rebeca Pérez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, 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, COVID Human Genetic Effort, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-, Biobank, NIAID-USUHS COVID Study Group, Bustamante, Jacinta, Froidure, Antoine

المساهمون: UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie

المصدر: Science immunology, Vol. 6, no. 62 (2021) (2021)

مصطلحات موضوعية: Adolescent, Adult, Aged, 80 and over, Alleles, COVID-19, Child, Preschool, Genetic Diseases, X-Linked, Humans, Immune System Diseases, Infant, Male, Middle Aged, Pedigree, Penetrance, Toll-Like Receptor 7, Young Adult

الوصف: 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 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 variants ( = 3.5 × 10). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (=2, 5 and 38 years), or moderate (=1, 5 years), severe (=1, 27 years), or critical (=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 variants in the male general population is < 6.5x10 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 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.

العلاقة: boreal:258538; http://hdl.handle.net/2078.1/258538Test; info:pmid/34413140; urn:EISSN:2470-9468

الإتاحة: https://doi.org/10.1126/sciimmunol.abl4348Test
http://hdl.handle.net/2078.1/258538Test

المؤلفون: 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, HatipoÄŸlu, 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, Christèle, Kyheng, 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, de Diego, Rebeca Pérez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, 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, COVID Human Genetic Effort, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-, Biobank, NIAID-USUHS COVID Study Group, 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, Froidure, Antoine

المساهمون: UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie

المصدر: Science immunology, Vol. 6, no.62, p. e (2021)

مصطلحات موضوعية: Adolescent, Adult, Aged, 80 and over, Alleles, COVID-19, Child, Preschool, Genetic Diseases, X-Linked, Humans, Immune System Diseases, Infant, Male, Middle Aged, Pedigree, Penetrance, Toll-Like Receptor 7, Young Adult

الوصف: 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 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 variants ( = 3.5 × 10). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (=2, 5 and 38 years), or moderate (=1, 5 years), severe (=1, 27 years), or critical (=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 variants in the male general population is < 6.5x10 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 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.

العلاقة: boreal:263114; http://hdl.handle.net/2078.1/263114Test; info:pmid/34413140; urn:ISSN:2470-9468; urn:EISSN:2470-9468

الإتاحة: https://doi.org/10.1126/sciimmunol.abl4348Test
http://hdl.handle.net/2078.1/263114Test