Articles producció científicaMedicina i Cirurgia

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

  • Identification data

    Identifier:  imarina:9229658
    Handle: https://hdl.handle.net/20.500.11797/imarina9229658
    Authors:  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, C I 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
    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 1202 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 x 10(-5)). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n = 2) or moderate (n = 1), severe (n = 1), or critical (n = 1) pneumonia. Two patients 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 <6.5 x 10(-4). We 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.

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    Link to the original source: https://www.science.org/doi/10.1126/sciimmunol.abl4348
    APA: Asano, Takaki; Boisson, Bertrand; Onodi, Fanny; Matuozzo, Daniela; Moncada-Velez, Marcela; Renkilaraj, Majistor Raj Luxman Maglorius; Zhang, Peng; Mee (2021). X-linked recessive TLR7 deficiency in similar to 1% of men under 60 years old with life-threatening COVID-19. Science Immunology, 6(62), eabl4348-. DOI: 10.1126/sciimmunol.abl4348
    Paper original source: Science Immunology. 6 (62): eabl4348-
    Article's DOI: 10.1126/sciimmunol.abl4348
    Journal publication year: 2021-08-19
    Entity: Universitat Rovira i Virgili
    Paper version: info:eu-repo/semantics/publishedVersion
    Record's date: 2026-03-02
    URV's Author/s: Auguet Quintillà, Maria Teresa
    Department: Medicina i Cirurgia
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Publication Type: Journal Publications
    Author, as appears in the article.: 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, C I 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
    Thematic Areas: Medicine (miscellaneous), Immunology and allergy, Immunology, General medicine
    Author's mail: mariateresa.auguet@urv.cat

  • Keywords:

    Toll-like receptors
    Subsets
    Single-stranded rna
    Redundant
    Recognition
    Pyogenic bacterial-infections
    Protective immunity
    Plasmacytoid dendritic cells
    Humans
    Host-defense
    Good health and well-being
    Immunology
    Immunology and Allergy
    Medicine (Miscellaneous)
    General medicine

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