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10.1126/sciimmunol.abl4348

http://scihub22266oqcxt.onion/10.1126/sciimmunol.abl4348
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34413140!8532080!34413140
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suck abstract from ncbi


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pmid34413140      Sci+Immunol 2021 ; 6 (62): ä
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  • X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19 #MMPMID34413140
  • Asano T; Boisson B; Onodi F; Matuozzo D; Moncada-Velez M; Maglorius Renkilaraj MRL; Zhang P; Meertens L; Bolze A; Materna M; Korniotis S; Gervais A; Talouarn E; Bigio B; Seeleuthner Y; Bilguvar K; Zhang Y; Neehus AL; Ogishi M; Pelham SJ; Le Voyer T; Rosain J; Philippot Q; Soler-Palacin P; Colobran R; Martin-Nalda A; Riviere JG; Tandjaoui-Lambiotte Y; Chaibi K; Shahrooei M; Darazam IA; Olyaei NA; Mansouri D; Hatipoglu N; Palabiyik F; Ozcelik T; Novelli G; Novelli A; Casari G; Aiuti A; Carrera P; Bondesan S; Barzaghi F; Rovere-Querini P; Tresoldi C; Franco JL; Rojas J; Reyes LF; Bustos IG; Arias AA; Morelle G; Christele K; Troya J; Planas-Serra L; Schluter A; Gut M; Pujol A; Allende LM; Rodriguez-Gallego C; Flores C; Cabrera-Marante O; Pleguezuelo DE; de Diego RP; Keles S; Aytekin G; Akcan OM; Bryceson YT; Bergman P; Brodin P; Smole D; Smith CIE; Norlin AC; Campbell TM; Covill LE; Hammarstrom L; Pan-Hammarstrom Q; Abolhassani H; Mane S; Marr N; Ata M; Al Ali F; Khan T; Spaan AN; Dalgard CL; Bonfanti P; Biondi A; Tubiana S; Burdet C; Nussbaum R; Kahn-Kirby A; Snow AL; Bustamante J; Puel A; Boisson-Dupuis S; Zhang SY; Beziat V; Lifton RP; Bastard P; Notarangelo LD; Abel L; Su HC; Jouanguy E; Amara A; Soumelis V; Cobat A; Zhang Q; Casanova JL
  • Sci Immunol 2021[Aug]; 6 (62): ä PMID34413140show ga
  • 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 x 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.
  • |Adolescent[MESH]
  • |Adult[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Alleles[MESH]
  • |COVID-19/*complications[MESH]
  • |Child[MESH]
  • |Child, Preschool[MESH]
  • |Genetic Diseases, X-Linked/*complications[MESH]
  • |Humans[MESH]
  • |Immune System Diseases/*complications[MESH]
  • |Infant[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Pedigree[MESH]
  • |Penetrance[MESH]
  • |Toll-Like Receptor 7/*deficiency/genetics[MESH]


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