| Literature DB >> 34413140 |
Takaki Asano1, Bertrand Boisson2,3,4, Fanny Onodi5, Daniela Matuozzo3,4, Marcela Moncada-Velez1, Majistor Raj Luxman Maglorius Renkilaraj3,4, Peng Zhang1, Laurent Meertens5, Alexandre Bolze6, Marie Materna3,4, Richard P Lifton7,8, Paul Bastard3,4, Luigi D Notarangelo9,10, Laurent Abel1,3,4, Helen C Su9,10,11, Emmanuelle Jouanguy1,3,4, Ali Amara5, Vassili Soumelis12,13, Aurélie Cobat1,3,4, Qian Zhang1, Jean-Laurent Casanova2,3,4,14, Sarantis Korniotis12, Adrian Gervais3,4, Estelle Talouarn3,4, Benedetta Bigio1, Yoann Seeleuthner3,4, Kaya Bilguvar7, Yu Zhang9,10, Anna-Lena Neehus3,4, Masato Ogishi1, Simon J Pelham1, Tom Le Voyer3,4, Jérémie Rosain3,4, Quentin Philippot3,4, Pere Soler-Palacín15,16,17, Roger Colobran17,18,19, Andrea Martin-Nalda15,16,17, Jacques G Rivière15,16,17, Yacine Tandjaoui-Lambiotte20,21, Khalil Chaïbi22,23, Mohammad Shahrooei24,25, Ilad Alavi Darazam26,27, Nasrin Alipour Olyaei24,25, Davood Mansouri28,29,30, Nevin Hatipoğlu31, Figen Palabiyik31, Tayfun Ozcelik32, Giuseppe Novelli33, Antonio Novelli34, Giorgio Casari35,36, Alessandro Aiuti35,37, Paola Carrera36, Simone Bondesan36, Federica Barzaghi37, Patrizia Rovere-Querini35,38, Cristina Tresoldi39, Jose Luis Franco40, Julian Rojas40, Luis Felipe Reyes41, Ingrid G Bustos41, Andres Augusto Arias1,40,42, Guillaume Morelle43, Kyheng Christèle43, Jesús Troya44, Laura Planas-Serra45,46, Agatha Schlüter45,46, Marta Gut47, Aurora Pujol45,46,48, Luis M Allende49,50, Carlos Rodriguez-Gallego51,52, Carlos Flores53,54,55,56, Oscar Cabrera-Marante49, Daniel E Pleguezuelo49, Rebeca Pérez de Diego57, Sevgi Keles58, Gokhan Aytekin59, Ozge Metin Akcan58, Yenan T Bryceson60, Peter Bergman61,62, Petter Brodin63, Daniel Smole64, C I Edvard Smith65,62, Anna-Carin Norlin62, Tessa M Campbell60, Laura E Covill60, Lennart Hammarström66, Qiang Pan-Hammarström66, Hassan Abolhassani66,67, Shrikant Mane68, Nico Marr69, Manar Ata69, Fatima Al Ali69, Taushif Khan69, András N Spaan1,70, Clifton L Dalgard71,72, Paolo Bonfanti73, Andrea Biondi74, Sarah Tubiana75,76, Charles Burdet75,77, Robert Nussbaum78, Amanda Kahn-Kirby78, Andrew L Snow79, Jacinta Bustamante1,3,4,80, Anne Puel1,3,4, Stéphanie Boisson-Dupuis1,3,4, Shen-Ying Zhang1,3,4, Vivien Béziat1,3,4.
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.Entities:
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Year: 2021 PMID： 34413140 PMCID： PMC8532080 DOI： 10.1126/sciimmunol.abl4348
Source DB: PubMed Journal: Sci Immunol ISSN： 2470-9468