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

Takaki Asano; Bertrand Boisson; Fanny Onodi; Daniela Matuozzo; Marcela Moncada-Velez; Majistor Raj Luxman Maglorius Renkilaraj; Peng Zhang; Laurent Meertens; Alexandre Bolze; Marie Materna; Sarantis Korniotis; Adrian Gervais; Estelle Talouarn; Benedetta Bigio; Yoann Seeleuthner; Kaya Bilguvar; Yu Zhang; Anna-Lena Neehus; Masato Ogishi; Simon J. Pelham; Tom Le Voyer; Jeremie Rosain; Quentin Philippot; Pere Soler-Palacin; Roger Colobran; Andrea Martin-Nalda; Jacques G. Riviere; Yacine Tandjaoui-Lambiotte; Khalil Chaibi; Mohammad Shahrooei; Ilad Alavi Darazam; Nasrin Alipour Olyaei; Davood Mansouri; Figen Palabiyik; Tayfun Ozcelik; Giuseppe Novelli; Antonio Novelli; Giorgio Casari; Alessandro Aiuti; Paola Carrera; Simone Bondesan; Federica Barzaghi; Patrizia Rovere-Querini; Cristina Tresoldi; Jose Luis Franco; Julian Rojas; Luis Felipe Reyes; Ingrid G. Bustos; Andres Augusto Arias; Guillaume Morelle; Christele Kyheng; Jesus Troya; Laura Planas-Serra; Agatha Schluter; Marta Gut; Aurora Pujol; Luis M. Allende; Carlos Rodriguez-Gallego; Carlos Flores; Oscar Cabrera-Marante; Daniel E. Pleguezuelo; Rebeca Perez de Diego; Sevgi Keles; Gokhan Aytekin; Ozge Metin Akcan; Yenan T. Bryceson; Peter Bergman; Petter Brodin; Daniel Smole; C. I. Edvard Smith; Anna-Carin Norlin; Tessa M. Campbell; Laura E. Covill; Lennart Hammarstrom; Qiang Pan-Hammarstrom; Hassan Abolhassani; Shrikant Mane; Nico Marr; Manar Ata; Fatima Al Ali; Taushif Khan; Andras N. Spaan; Clifton L. Dalgard; Paolo Bonfanti; Andrea Biondi; Sarah Tubiana; Charles Burdet; Robert Nussbaum; Amanda Kahn-Kirby; Andrew L. Snow; Jacinta Bustamante; Anne Puel; Stephanie Boisson-Dupuis; Shen-Ying Zhang; Vivien Beziat; Richard P. Lifton; Paul Bastard; Luigi D. Notarangelo; Laurent Abel; Helen C. Su; Emmanuelle Jouanguy; Ali Amara; Vassili Soumelis; Aurelie Cobat; Qian Zhang; Jean-Laurent Casanova; Amsterdam UMC Covid-19 Biobank; Cyril Cyrus

doi:10.1126/sciimmunol.abl4348

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

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

Takaki Asano, Bertrand Boisson, Fanny Onodi, Daniela Matuozzo, Marcela Moncada-Velez, Majistor Raj Luxman Maglorius Renkilaraj, Peng Zhang, Laurent Meertens, Alexandre Bolze, Marie Materna, …

Science immunology, Vol.6(62)

01/08/2021

DOI: https://doi.org/10.1126/sciimmunol.abl4348

PMID: 34413140

Abstract

Immunology

Life Sciences & Biomedicine

Science & Technology

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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Title: X-linked recessive TLR7 deficiency in similar to 1% of men under 60 years old with life-threatening COVID-19
Creators - without role: Takaki Asano - Rockefeller University
Bertrand Boisson - Rockefeller University
Fanny Onodi - Université Paris Cité
Daniela Matuozzo - Necker Hosp Sick Children, INSERM U1163, Necker Branch, Lab Human Genet Infect Dis, Paris, France
Marcela Moncada-Velez - Rockefeller University
Majistor Raj Luxman Maglorius Renkilaraj - Necker Hosp Sick Children, INSERM U1163, Necker Branch, Lab Human Genet Infect Dis, Paris, France
Peng Zhang - Rockefeller University
Laurent Meertens - Université Paris Cité
Alexandre Bolze - Helix
Marie Materna - Necker Hosp Sick Children, INSERM U1163, Necker Branch, Lab Human Genet Infect Dis, Paris, France
Sarantis Korniotis - Université Paris Cité
Adrian Gervais - Inserm
Estelle Talouarn - Necker Hosp Sick Children, INSERM U1163, Necker Branch, Lab Human Genet Infect Dis, Paris, France
Benedetta Bigio - Rockefeller University
Yoann Seeleuthner - Necker Hosp Sick Children, INSERM U1163, Necker Branch, Lab Human Genet Infect Dis, Paris, France
Kaya Bilguvar - Supreme Council Of Health
Yu Zhang - NIAID, Lab Clin Immunol & Microbiol, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
Anna-Lena Neehus - Necker Hosp Sick Children, INSERM U1163, Necker Branch, Lab Human Genet Infect Dis, Paris, France
Masato Ogishi - Rockefeller University
Simon J. Pelham - Rockefeller University
Tom Le Voyer - Inserm
Jeremie Rosain - Inserm
Quentin Philippot - Inserm
Pere Soler-Palacin - Vall dHebron Univ Hosp HUVH, Vall dHebron Res Inst VHIR, Infect Immunocompromised Pediat Patients Res Grp, Vall dHebron Barcelona Hosp Campus, Barcelona, Catalonia, Spain
Roger Colobran - Jeffrey Modell Diagnost & Res Ctr Primary Immunod, Barcelona, Catalonia, Spain
Andrea Martin-Nalda - Vall dHebron Univ Hosp HUVH, Vall dHebron Res Inst VHIR, Infect Immunocompromised Pediat Patients Res Grp, Vall dHebron Barcelona Hosp Campus, Barcelona, Catalonia, Spain
Jacques G. Riviere - Vall dHebron Univ Hosp HUVH, Vall dHebron Res Inst VHIR, Infect Immunocompromised Pediat Patients Res Grp, Vall dHebron Barcelona Hosp Campus, Barcelona, Catalonia, Spain
Yacine Tandjaoui-Lambiotte - Assistance Publique – Hôpitaux de Paris
Khalil Chaibi - Assistance Publique – Hôpitaux de Paris
Mohammad Shahrooei - Sina
Ilad Alavi Darazam - Shahid Beheshti University
Nasrin Alipour Olyaei - Sina
Davood Mansouri - Shahid Beheshti University
Figen Palabiyik - Univ Hlth Sci, Bakirkoy Dr Sadi Konuk Training & Res Hosp, Pediat Infect Dis Unit, Istanbul, Turkey
Tayfun Ozcelik - Bilkent University
Giuseppe Novelli - Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy
Antonio Novelli - College Station Medical Center
Giorgio Casari - Mylan
Alessandro Aiuti - Mylan
Paola Carrera - Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Simone Bondesan - Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Federica Barzaghi - Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Patrizia Rovere-Querini - Univ Vita Salute San Raffaele, Milan, Italy
Cristina Tresoldi - IRCCS Osped San Raffaele, Mol Hematol Unit, Milan, Italy
Jose Luis Franco - Universidad de Antioquia
Julian Rojas - Universidad de Antioquia
Luis Felipe Reyes - Univ La Sabana, Chia, Colombia
Ingrid G. Bustos - Univ La Sabana, Chia, Colombia
Andres Augusto Arias - Rockefeller University
Guillaume Morelle - University of Paris-Saclay
Christele Kyheng - University of Paris-Saclay
Jesus Troya - College Station Medical Center
Laura Planas-Serra - Biomed Research Institute
Agatha Schluter - Biomed Research Institute
Marta Gut - Barcelona Inst Sci & Technol BIST, Ctr Genom Regulat CRG, CNAG CRG, Baldiri Reixac 4, Barcelona 08028, Spain
Aurora Pujol - Biomed Research Institute
Luis M. Allende - Univ Hosp 12 Octubre, Res Inst Hosp 12 Octubre 1 12, Immunol Dept, Madrid, Spain
Carlos Rodriguez-Gallego - Univ Hosp Gran Canaria Dr Negrin, Dept Immunol, Canarian Hlth Syst, Las Palmas Gran Canaria, Spain
Carlos Flores - ITER
Oscar Cabrera-Marante - Univ Hosp 12 Octubre, Res Inst Hosp 12 Octubre 1 12, Immunol Dept, Madrid, Spain
Daniel E. Pleguezuelo - Univ Hosp 12 Octubre, Res Inst Hosp 12 Octubre 1 12, Immunol Dept, Madrid, Spain
Rebeca Perez de Diego - Univ Hosp La Paz, IdiPAZ Inst Hlth Res, Lab Immunogenet Human Dis, Madrid, Spain
Sevgi Keles - Necmettin Erbakan University
Gokhan Aytekin - Konya City Hosp, Div Allergy & Immunol, Konya, Turkey
Ozge Metin Akcan - Necmettin Erbakan University
Yenan T. Bryceson - Karolinska Institutet
Peter Bergman - Karolinska Institutet
Petter Brodin - Life Lab
Daniel Smole - Intens
C. I. Edvard Smith - Karolinska Univ Hosp, Immunodeficiency Unit, Infect Dis Clin, Stockholm, Sweden
Anna-Carin Norlin - Karolinska Univ Hosp, Immunodeficiency Unit, Infect Dis Clin, Stockholm, Sweden
Tessa M. Campbell - Karolinska Institutet
Laura E. Covill - Karolinska Institutet
Lennart Hammarstrom - Karolinska Institutet
Qiang Pan-Hammarstrom - Karolinska Institutet
Hassan Abolhassani - Karolinska Institutet
Shrikant Mane - Yale University
Nico Marr - College Station Medical Center
Manar Ata - College Station Medical Center
Fatima Al Ali - College Station Medical Center
Taushif Khan - College Station Medical Center
Andras N. Spaan - Rockefeller University
Clifton L. Dalgard - Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA
Paolo Bonfanti - University of Milano-Bicocca
Andrea Biondi - University of Milan
Sarah Tubiana - Inserm
Charles Burdet - Inserm
Robert Nussbaum - Invitae
Amanda Kahn-Kirby - Invitae
Andrew L. Snow - Uniformed Serv Univ Hlth Sci, Dept Pharmacol & Mol Therapeut, Bethesda, MD 20814 USA
Jacinta Bustamante - Rockefeller University
Anne Puel - Rockefeller University
Stephanie Boisson-Dupuis - Rockefeller University
Shen-Ying Zhang - Rockefeller University
Vivien Beziat - Rockefeller University
Richard P. Lifton - Supreme Council Of Health
Paul Bastard - Rockefeller University
Luigi D. Notarangelo - NIAID, Lab Clin Immunol & Microbiol, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
Laurent Abel - Rockefeller University
Helen C. Su - NIAID, Lab Clin Immunol & Microbiol, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
Emmanuelle Jouanguy - Rockefeller University
Ali Amara - Université Paris Cité
Vassili Soumelis - Université Paris Cité
Aurelie Cobat - Rockefeller University
Qian Zhang - Rockefeller University
Jean-Laurent Casanova - Rockefeller University
Amsterdam UMC Covid-19 Biobank
Cyril Cyrus - Imam Abdulrahman Bin Faisal University
Publication Details: Science immunology, Vol.6(62)
Publisher: Amer Assoc Advancement Science
Number of pages: 22
Grant note: UL1TR001866 / NIH Clinical and Translational Science Award (CTSA) program; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) Howard Hughes Medical Institute, Rockefeller University OA18/017 / Fundacion DISA Meyer Foundation FRM; Fondation pour la Recherche Medicale EQU202003010193 / FRM; Fondation pour la Recherche Medicale ANR-10-IAHU-01; ANR-10-LABX-62-IBEID / French National Research Agency (ANR) Fast Grant from Emergent Ventures ANR-20-CO11-0001 / ANR AABIFNCOV; French National Research Agency (ANR) Grandir-Fonds de solidarite pour l'enfance Mercatus Center at the George Mason University University of Paris Institut National de la Sante et de la Recherche Medicale (INSERM); Institut National de la Sante et de la Recherche Medicale (Inserm) intramural COVID Host Genetics program University of Paris PLAN D'URGENCE COVID19 French Ministry of Health REACTing-INSERM Cabildo Insular de Tenerife ("Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19") REACTing consortium ANR-10-LABX-62-IBEID / Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence COVID-2020-12371617 / Italian Ministry of Health; Ministry of Health, Italy Fisher Center for Alzheimer's Research Foundation ANR-10-IAHU-01; ANR-20-COVI-000; ANR-20-CO11-0004 / ANR; French National Research Agency (ANR) Yale Center for Mendelian Genomics CGIEU0000219140 / Cabildo Insular de Tenerife 806-2018 / Cooperation Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX) JPB Foundation ANR-17-CE15-0003-01 / ANR APCOD; French National Research Agency (ANR) Mercatus Center ANR-17-CE15-0003 / ANR DENDRISEPSIS; French National Research Agency (ANR) SCOR Corporate Foundation for Science (PHRC 20-0424 / French Ministry of Health Square Foundation NPRP9-251-3-045 / Qatar National Research Fund; Qatar National Research Fund (QNRF) St. Giles Foundation UM1HG006504; U24HG008956 / GSP Coordinating Center - National Human Genome Research Institute (NHGRI) 713-2016; 111574455633 / Colciencias; Departamento Administrativo de Ciencia, Tecnologia e Innovacion Colciencias Fondation du Souffle 824110 / European Union; European Commission EQU201903007798 / French Foundation for Medical Research (FRM); Fondation pour la Recherche Medicale International PhD program of the Imagine Institute National Center for Advancing Translational Sciences (NCATS); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) INSERM; Institut National de la Sante et de la Recherche Medicale (Inserm) R01AI088364 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA ANR-20-CE93-003 / ANR GENVIR; French National Research Agency (ANR) RTC-2017-6471-1 / Spanish Ministry of Science and Innovation (AEI/FEDER, UE); Spanish Government 1ZIAAI001265; ZIA AI001270 / Division of Intramural Research, NIAID, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Center for Medical Innovation (CIMED) Swedish Medical Research Council; Swedish Medical Research Council (SMRC) Bettencourt Schueller Foundation ANR GENCOVID project; French National Research Agency (ANR) RECOVER WP 6 / European Commission; European Commission Joint Research Centre 824110 COVID-19/PID12342 / European Union's Horizon 2020 Research and Innovation Program (EasiGenomics grant) SDR400048 / Sidra Medicine RACPL20FIR01-COVIDSOUL / University of Paris (Plan de Soutien Covid-19) Stockholm County Council (ALF-project); Stockholm County Council COV20_01333; COV20_01334 / Instituto de Salud Carlos III
Identifiers: 9915837308331
Academic Unit: Imam Abdulrahman Bin Faisal University
Language: English
Resource Type: Journal article