Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/180375
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))

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