Title: | 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 Lifton, Richard P. Bastard, Paul Abel, Laurent Jouanguy, Emmanuelle Amara, Ali Soumelis, Vassili Cobat, Aurélie Zhang, Qian Casanova, Jean-Laurent COVID Human Genetic Effort French COVID Cohort Study Group COVID-STORM Clinicians Amsterdam UMC Covid-19 Biobank COVID Clinicians Gervais, Adrian Imagine COVID Group CoV-Contact Cohort NIAID-USUHS COVID Study Group Talouarn, Estelle Bigio, Benedetta Seeleuthner, Yoann Bilguvar, Kaya Zhang, Yu Neehus, Anna-Lena Ogishi, Masato Soler Palacín, Pere Pelham, Simon J. Martin Nalda, Andrea Le Voyer, Tom Rosain, Jérémie Philippot, Quentin Colobran, Roger Rivière, Jacques G. Tandjaoui-Lambiotte, Yacine Chaïbi, Khalil Shahrooei, Mohammad Darazam, Ilad Alavi Olyaei, Nasrin Alipour Mansouri, Davood Hatipoğlu, Nevin Casari, Giorgio Palabiyik, Figen Carrera, Paola Ozcelik, Tayfun Novelli, Giuseppe Novelli, Antonio Aiuti, Alessandro Bondesan, Simone Barzaghi, Federica Rovere-Querini, Patrizia Tresoldi, Cristina Franco, Jose Luis Rojas, Julian Reyes, Luis Felipe Bustos, Ingrid G. Planas Serra, Laura Arias, Andres Augusto Gut, Marta Morelle, Guillaume Christèle, Kyheng Troya, Jesús Schlüter, Agatha Pujol, Aurora Allende, Luis M. Rodriguez Gallego, Carlos Flores, Carlos Cabrera Marante, Oscar Pleguezuelo, Daniel E. Pérez de Diego, Rebeca Keles, Sevgi Brodin, Petter Aytekin, Gokhan Smith, C.I. Edvard Akcan, Ozge Metin Bryceson, Yenan T. Bergman, Peter Smole, Daniel Norlin, Anna-Carin Campbell, Tessa M. Covill, Laura E. Hammarström, Lennart Pan-Hammarström, Qiang Abolhassani, Hassan Mane, Shrikant Marr, Nico Dalgard, Clifton L. Ata, Manar Biondi, Andrea Al Ali, Fatima Khan, Taushif Spaan, András N. Bonfanti, Paolo Tubiana, Sarah Burdet, Charles Nussbaum, Robert L. Kahn-Kirby, Amanda Snow, Andrew L. Bustamante, Jacinta Puel, Anne Boisson-Dupuis, Stéphanie Notarangelo, Luigi D. Zhang, Shen-Ying Su, Helen C. Béziat, Vivien |
Keywords: | COVID-19 Proteïnes Resposta immunitària COVID-19 Proteins Immune response |
Issue Date: | 19-Aug-2021 |
Publisher: | American Association for the Advancement of Science (AAAS) |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1126/sciimmunol.abl4348 |
It is part of: | Science Immunology, 2021, vol. 6, num. 62 |
URI: | http://hdl.handle.net/2445/180375 |
Related resource: | https://doi.org/10.1126/sciimmunol.abl4348 |
ISSN: | 2470-9468 |
Appears in Collections: | Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
|