Your browser doesn't support javascript.
X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.
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; Gervais, Adrian; Talouarn, Estelle; Bigio, Benedetta; Seeleuthner, Yoann; Bilguvar, Kaya; Zhang, Yu; Neehus, Anna-Lena; Ogishi, Masato; Pelham, Simon J; Le Voyer, Tom; Rosain, Jérémie; Philippot, Quentin; Soler-Palacín, Pere; Colobran, Roger; Martin-Nalda, Andrea; Rivière, Jacques G; Tandjaoui-Lambiotte, Yacine; Chaïbi, Khalil; Shahrooei, Mohammad; Darazam, Ilad Alavi; Olyaei, Nasrin Alipour; Mansouri, Davood; Hatipoglu, Nevin; Palabiyik, Figen; Ozcelik, Tayfun; Novelli, Giuseppe; Novelli, Antonio; Casari, Giorgio; Aiuti, Alessandro; Carrera, Paola; Bondesan, Simone; Barzaghi, Federica; Rovere-Querini, Patrizia; Tresoldi, Cristina; Franco, Jose Luis; Rojas, Julian; Reyes, Luis Felipe; Bustos, Ingrid G; Arias, Andres Augusto.
  • Asano T; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Boisson B; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. casanova@rockefeller.edu bebo283@rockefeller.edu.
  • Onodi F; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Matuozzo D; University of Paris, Imagine Institute, Paris, France.
  • Moncada-Velez M; Laboratory of Genomes & Cell Biology of Disease, INSERM U944, CNRS UMR7212, University of Paris, Research Institute of Saint-Louis, Saint-Louis Hospital, Paris, France.
  • Maglorius Renkilaraj MRL; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Zhang P; University of Paris, Imagine Institute, Paris, France.
  • Meertens L; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Bolze A; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Materna M; University of Paris, Imagine Institute, Paris, France.
  • Korniotis S; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Gervais A; Laboratory of Genomes & Cell Biology of Disease, INSERM U944, CNRS UMR7212, University of Paris, Research Institute of Saint-Louis, Saint-Louis Hospital, Paris, France.
  • Talouarn E; Helix, San Mateo, CA, USA.
  • Bigio B; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Seeleuthner Y; University of Paris, Imagine Institute, Paris, France.
  • Bilguvar K; University of Paris, INSERM U976, F-75006 Paris, France.
  • Zhang Y; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Neehus AL; University of Paris, Imagine Institute, Paris, France.
  • Ogishi M; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Pelham SJ; University of Paris, Imagine Institute, Paris, France.
  • Le Voyer T; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Rosain J; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Philippot Q; University of Paris, Imagine Institute, Paris, France.
  • Soler-Palacín P; Yale Center for Genome Analysis and Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
  • Colobran R; Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA.
  • Martin-Nalda A; NIAID Clinical Genomics Program, NIH, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA.
  • Rivière JG; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Tandjaoui-Lambiotte Y; University of Paris, Imagine Institute, Paris, France.
  • Chaïbi K; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Shahrooei M; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Darazam IA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Olyaei NA; University of Paris, Imagine Institute, Paris, France.
  • Mansouri D; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Hatipoglu N; University of Paris, Imagine Institute, Paris, France.
  • Palabiyik F; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Ozcelik T; University of Paris, Imagine Institute, Paris, France.
  • Novelli G; Infection in Immunocompromised Pediatric Patients Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia Spain.
  • Novelli A; Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona (UAB), Barcelona, Catalonia, Spain.
  • Casari G; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.
  • Aiuti A; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.
  • Carrera P; Diagnostic Immunology Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.
  • Bondesan S; Immunology Division, Genetics Department, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona (UAB), Barcelona, Catalonia, Spain.
  • Barzaghi F; Infection in Immunocompromised Pediatric Patients Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia Spain.
  • Rovere-Querini P; Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona (UAB), Barcelona, Catalonia, Spain.
  • Tresoldi C; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.
  • Franco JL; Infection in Immunocompromised Pediatric Patients Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia Spain.
  • Rojas J; Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona (UAB), Barcelona, Catalonia, Spain.
  • Reyes LF; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.
  • Bustos IG; AP-HP, Avicenne Hospital, Intensive Care Unit, Bobigny, France.
  • Arias AA; INSERM U1272 Hypoxia & Lung, Bobigny, France.
Sci Immunol ; 6(62)2021 08 19.
Статья в английский | MEDLINE | ID: covidwho-1434876
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.
Тема - темы

Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Genetic Diseases, X-Linked / Toll-Like Receptor 7 / COVID-19 / Immune System Diseases Тип исследования: Когортное исследование / Изучение этиологии / Наблюдательное исследование / Прогностическое исследование Темы: Длинный Ковид / Варианты Пределы темы: Подростки / Взрослые / Пожилые / Дети / Детский дошкольный / Люди / Грудные дети / Мужчины / Middle aged / Молодой взрослый Язык: английский Год: 2021 Тип: Статья Аффилированная страна: Sciimmunol.abl4348

Документы, близкие по теме

MEDLINE

...
LILACS

LIS


Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Genetic Diseases, X-Linked / Toll-Like Receptor 7 / COVID-19 / Immune System Diseases Тип исследования: Когортное исследование / Изучение этиологии / Наблюдательное исследование / Прогностическое исследование Темы: Длинный Ковид / Варианты Пределы темы: Подростки / Взрослые / Пожилые / Дети / Детский дошкольный / Люди / Грудные дети / Мужчины / Middle aged / Молодой взрослый Язык: английский Год: 2021 Тип: Статья Аффилированная страна: Sciimmunol.abl4348