X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.
X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.
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DOI：
10.1126/sciimmunol.abl4348
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发表时间：
2021-08-19
影响因子：
24.8
通讯作者：
Casanova JL
中科院分区：
文献类型：
--
作者：
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-Palacín P;Colobran R;Martin-Nalda A;Rivière JG;Tandjaoui-Lambiotte Y;Chaïbi K;Shahrooei M;Darazam IA;Olyaei NA;Mansouri D;Hatipoğlu 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;Christèle K;Troya J;Planas-Serra L;Schlüter 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;Hammarström L;Pan-Hammarström 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;COVID Human Genetic Effort;COVID-STORM Clinicians;COVID Clinicians;Imagine COVID Group;French COVID Cohort Study Group;CoV-Contact Cohort;Amsterdam UMC Covid-;Biobank;NIAID-USUHS COVID Study Group;Bustamante J;Puel A;Boisson-Dupuis S;Zhang SY;Béziat V;Lifton RP;Bastard P;Notarangelo LD;Abel L;Su HC;Jouanguy E;Amara A;Soumelis V;Cobat A;Zhang Q;Casanova JL
I型IFN免疫的常染色体先天性错误和针对这些细胞因子的自身抗体是至少10%的重症COVID-19肺炎病例的基础。我们报告了来自1，202名年龄为0.5至99岁（平均年龄：52.9岁）的不明原因重症COVID-19肺炎男性患者队列的16名年龄为7至71岁（平均年龄：36.7岁）的无关男性个体中非常罕见的、生化有害的X连锁TLR 7变体。331名年龄在1.3至102岁（平均年龄：38.7岁）的无症状或轻度感染的男性受试者中没有一人携带这种TLR 7变体（p = 3.5 × 10−5）。感染SARS-CoV-2的指示病例的5个半合子亲属的表型包括无症状或轻度感染（n=2，5和38岁），或中度（n=1，5岁），重度（n=1，27岁）或危重（n=1，29岁）肺炎。来自262名患有严重COVID-19肺炎的男性患者（平均年龄：51.0岁）的队列的两名男孩（7岁和12岁）对于有害的TLR 7变体是半合子的。在男性一般人群中，有害TLR 7变异体的累积等位基因频率< 6.5x10−4。我们还表明，血液B细胞系和骨髓细胞亚群的患者不响应TLR 7刺激，野生型TLR 7拯救的表型。患者的血液浆细胞样树突状细胞（pDC）产生低水平的I型IFN以响应SARS-CoV-2。总体而言，X连锁隐性TLR 7缺乏症是重症COVID-19肺炎的高度外显遗传病因，约1.8%的60岁以下男性患者存在这种情况。人TLR 7和pDCs对呼吸道中抗SARS-CoV-2的I型IFN保护性免疫是必需的。TLR 7和浆细胞样树突状细胞对于肺部针对SARS-CoV-2的I型IFN依赖性免疫至关重要。
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. TLR7 and plasmacytoid dendritic cells are essential for type I IFN-dependent immunity to SARS-CoV-2 in the lungs.
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危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.1126/science.aaa1578
发表时间：
2015-04-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ciancanelli MJ;Huang SX;Luthra P;Garner H;Itan Y;Volpi S;Lafaille FG;Trouillet C;Schmolke M;Albrecht RA;Israelsson E;Lim HK;Casadio M;Hermesh T;Lorenzo L;Leung LW;Pedergnana V;Boisson B;Okada S;Picard C;Ringuier B;Troussier F;Chaussabel D;Abel L;Pellier I;Notarangelo LD;García-Sastre A;Basler CF;Geissmann F;Zhang SY;Snoeck HW;Casanova JL
通讯作者：
Casanova JL
DOI：
10.1084/jem.20210554
发表时间：
2021-07-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bastard P;Orlova E;Sozaeva L;Lévy R;James A;Schmitt MM;Ochoa S;Kareva M;Rodina Y;Gervais A;Le Voyer T;Rosain J;Philippot Q;Neehus AL;Shaw E;Migaud M;Bizien L;Ekwall O;Berg S;Beccuti G;Ghizzoni L;Thiriez G;Pavot A;Goujard C;Frémond ML;Carter E;Rothenbuhler A;Linglart A;Mignot B;Comte A;Cheikh N;Hermine O;Breivik L;Husebye ES;Humbert S;Rohrlich P;Coaquette A;Vuoto F;Faure K;Mahlaoui N;Kotnik P;Battelino T;Trebušak Podkrajšek K;Kisand K;Ferré EMN;DiMaggio T;Rosen LB;Burbelo PD;McIntyre M;Kann NY;Shcherbina A;Pavlova M;Kolodkina A;Holland SM;Zhang SY;Crow YJ;Notarangelo LD;Su HC;Abel L;Anderson MS;Jouanguy E;Neven B;Puel A;Casanova JL;Lionakis MS
通讯作者：
Lionakis MS
影响因子：
30.5
作者：
Alculumbre, Solana G.;Saint-Andre, Violaine;Soumelis, Vassili
通讯作者：
Soumelis, Vassili