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Article Dans Une Revue Science Immunology Année : 2021

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

Mathieu P Rodero (1) , Takaki Asano , Bertrand Boisson (2) , Fanny Onodi , Daniela Matuozzo , Marcela Moncada-Velez , Majistor Raj Luxman Maglorius Renkilaraj (2) , Peng Zhang (3) , Laurent Meertens (4) , Alexandre Bolze (5) , Marie Materna (6) , Sarantis Korniotis , Adrian Gervais , Estelle Talouarn , Benedetta Bigio , Yoann Seeleuthner , Kaya Bilguvar , Yu Zhang , Anna-Lena Neehus , Masato Ogishi , Simon Pelham , Tom Le Voyer , Jérémie Rosain , Quentin Philippot , Pere Soler-Palacín , Roger Colobran , Andrea Martin-Nalda , Jacques Rivière , Yacine Tandjaoui-Lambiotte , Khalil Chaïbi , Mohammad Shahrooei , Ilad Alavi Darazam , Nasrin Alipour Olyaei , Davood Mansouri , Nevin Hatipoğlu , 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 Bustos , Andres Augusto Arias , Guillaume Morelle , Christèle Kyheng , Jesús Troya , Laura Planas-Serra , Agatha Schlüter , Marta Gut , Aurora Pujol , Luis Allende , Carlos Rodriguez-Gallego , Carlos Flores , Oscar Cabrera-Marante , Daniel Pleguezuelo , Rebeca Pérez de Diego , Sevgi Keles , Gokhan Aytekin , Ozge Metin Akcan , Yenan Bryceson , Peter Bergman , Petter Brodin , Daniel Smole , C. Smith , Anna-Carin Norlin , Tessa Campbell , Laura Covill , Lennart Hammarström , Qiang Pan-Hammarström , Hassan Abolhassani , Shrikant Mane , Nico Marr , Manar Ata , Fatima Al Ali , Taushif Khan , András Spaan , Clifton Dalgard , Paolo Bonfanti , Andrea Biondi , Sarah Tubiana , Charles Burdet , Robert Nussbaum , Amanda Kahn-Kirby , Andrew Snow , Jacinta Bustamante , Anne Puel , Stéphanie Boisson-Dupuis , Shen-Ying Zhang , Vivien Béziat , Richard Lifton , Paul Bastard , Luigi Notarangelo , Laurent Abel , Helen Su , Emmanuelle Jouanguy , Ali Amara , Vassili Soumelis , Aurélie Cobat , Qian Zhang , Jean-Laurent Casanova , French Covid Cohort Study Group (7, 8) , Claire Andréjak (9, 10, 11)
Takaki Asano
Fanny Onodi
Daniela Matuozzo
Marcela Moncada-Velez
Peng Zhang
Alexandre Bolze
Sarantis Korniotis
  • Fonction : Auteur
  • PersonId : 775864
  • IdRef : 179486225
Adrian Gervais
Estelle Talouarn
Benedetta Bigio
Yoann Seeleuthner
Kaya Bilguvar
Yu Zhang
  • Fonction : Auteur
Anna-Lena Neehus
Masato Ogishi
Simon Pelham
Tom Le Voyer
Jérémie Rosain
Quentin Philippot
  • Fonction : Auteur
Pere Soler-Palacín
Roger Colobran
Andrea Martin-Nalda
Jacques Rivière
Yacine Tandjaoui-Lambiotte
Khalil Chaïbi
  • Fonction : Auteur
Mohammad Shahrooei
Ilad Alavi Darazam
Nasrin Alipour Olyaei
Davood Mansouri
Nevin Hatipoğlu
Figen Palabiyik
Tayfun Ozcelik
Giuseppe Novelli
Antonio Novelli
  • Fonction : Auteur
Giorgio Casari
Alessandro Aiuti
Paola Carrera
  • Fonction : Auteur
Simone Bondesan
Federica Barzaghi
Patrizia Rovere-Querini
  • Fonction : Auteur
Cristina Tresoldi
  • Fonction : Auteur
Jose Luis Franco
Julian Rojas
Luis Felipe Reyes
Ingrid Bustos
Andres Augusto Arias
Guillaume Morelle
Christèle Kyheng
Jesús Troya
Laura Planas-Serra
Agatha Schlüter
Marta Gut
Aurora Pujol
Luis Allende
Carlos Rodriguez-Gallego
Carlos Flores
Oscar Cabrera-Marante
Daniel Pleguezuelo
Rebeca Pérez de Diego
Sevgi Keles
Gokhan Aytekin
Ozge Metin Akcan
  • Fonction : Auteur
Yenan Bryceson
Peter Bergman
Petter Brodin
Daniel Smole
C. Smith
Anna-Carin Norlin
Tessa Campbell
Laura Covill
Lennart Hammarström
Qiang Pan-Hammarström
Hassan Abolhassani
Shrikant Mane
Nico Marr
Manar Ata
Fatima Al Ali
Taushif Khan
András Spaan
Clifton Dalgard
Paolo Bonfanti
Andrea Biondi
  • Fonction : Auteur
Sarah Tubiana
Charles Burdet
  • Fonction : Auteur
Robert Nussbaum
Amanda Kahn-Kirby
Andrew Snow
Jacinta Bustamante
Anne Puel
Stéphanie Boisson-Dupuis
Shen-Ying Zhang
Vivien Béziat
Richard Lifton
  • Fonction : Auteur
Paul Bastard
Luigi Notarangelo
Laurent Abel
Helen Su
Emmanuelle Jouanguy
Ali Amara
  • Fonction : Auteur
Vassili Soumelis
Aurélie Cobat
Qian Zhang
Jean-Laurent Casanova

Résumé

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 × 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 × 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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Dates et versions

hal-03367639 , version 1 (31-05-2022)

Identifiants

Citer

Mathieu P Rodero, Takaki Asano, Bertrand Boisson, Fanny Onodi, Daniela Matuozzo, et al.. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Science Immunology, 2021, 6 (62), ⟨10.1126/sciimmunol.abl4348⟩. ⟨hal-03367639⟩
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