| Title: |
X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19 |
| Authors: |
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; Khan, Taushif; Spaan, András N.; Bonfanti, Paolo; Tubiana, Sarah; Burdet, Charles; Nussbaum, Robert L.; Kahn-Kirby, Amanda; Snow, Andrew L.; Bustamante, Jacinta; Puel, Anne; Lifton, Richard P.; Boisson-Dupuis, Stéphanie; Notarangelo, Luigi D.; Zhang, Shen-Ying; Su, Helen C.; Béziat, Vivien; 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, 1968-; 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 |
| Source: |
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
| Publisher Information: |
American Association for the Advancement of Science (AAAS) |
| Publication Year: |
2021 |
| Collection: |
Dipòsit Digital de la Universitat de Barcelona |
| Subject Terms: |
COVID-19; Proteïnes; Resposta immunitària; Proteins; Immune response |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
22 p.; application/pdf |
| Language: |
English |
| Relation: |
Reproducció del document publicat a: https://doi.org/10.1126/sciimmunol.abl4348; Science Immunology, 2021, vol. 6, num. 62; https://doi.org/10.1126/sciimmunol.abl4348; info:eu-repo/grantAgreement/EC/H2020/824110/EU//EASI-Genomics; https://hdl.handle.net/2445/180375 |
| Availability: |
https://hdl.handle.net/2445/180375 |
| Rights: |
cc by (c) Asano, Takaki et al, 2021 ; http://creativecommons.org/licenses/by/3.0/es/ ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.F34E4317 |
| Database: |
BASE |