Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths.
Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths.
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DOI：
10.1126/sciimmunol.abl4340
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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：
Bastard P;Gervais A;Le Voyer T;Rosain J;Philippot Q;Manry J;Michailidis E;Hoffmann HH;Eto S;Garcia-Prat M;Bizien L;Parra-Martínez A;Yang R;Haljasmägi L;Migaud M;Särekannu K;Maslovskaja J;de Prost N;Tandjaoui-Lambiotte Y;Luyt CE;Amador-Borrero B;Gaudet A;Poissy J;Morel P;Richard P;Cognasse F;Troya J;Trouillet-Assant S;Belot A;Saker K;Garçon P;Rivière JG;Lagier JC;Gentile S;Rosen LB;Shaw E;Morio T;Tanaka J;Dalmau D;Tharaux PL;Sene D;Stepanian A;Megarbane B;Triantafyllia V;Fekkar A;Heath JR;Franco JL;Anaya JM;Solé-Violán J;Imberti L;Biondi A;Bonfanti P;Castagnoli R;Delmonte OM;Zhang Y;Snow AL;Holland SM;Biggs C;Moncada-Vélez M;Arias AA;Lorenzo L;Boucherit S;Coulibaly B;Anglicheau D;Planas AM;Haerynck F;Duvlis S;Nussbaum RL;Ozcelik T;Keles S;Bousfiha AA;El Bakkouri J;Ramirez-Santana C;Paul S;Pan-Hammarström Q;Hammarström L;Dupont A;Kurolap A;Metz CN;Aiuti A;Casari G;Lampasona V;Ciceri F;Barreiros LA;Dominguez-Garrido E;Vidigal M;Zatz M;van de Beek D;Sahanic S;Tancevski I;Stepanovskyy Y;Boyarchuk O;Nukui Y;Tsumura M;Vidaur L;Tangye SG;Burrel S;Duffy D;Quintana-Murci L;Klocperk A;Kann NY;Shcherbina A;Lau YL;Leung D;Coulongeat M;Marlet J;Koning R;Reyes LF;Chauvineau-Grenier A;Venet F;Monneret G;Nussenzweig MC;Arrestier R;Boudhabhay I;Baris-Feldman H;Hagin D;Wauters J;Meyts I;Dyer AH;Kennelly SP;Bourke NM;Halwani R;Sharif-Askari NS;Dorgham K;Sallette J;Sedkaoui SM;AlKhater S;Rigo-Bonnin R;Morandeira F;Roussel L;Vinh DC;Ostrowski SR;Condino-Neto A;Prando C;Bonradenko A;Spaan AN;Gilardin L;Fellay J;Lyonnet S;Bilguvar K;Lifton RP;Mane S;HGID Lab;COVID Clinicians;COVID-STORM Clinicians;NIAID Immune Response to COVID Group;NH-COVAIR Study Group;Danish CHGE;Danish Blood Donor Study;St. James's Hospital;SARS CoV2 Interest group;French COVID Cohort Study Group;Imagine COVID-Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19;Biobank Investigators;COVID Human Genetic Effort;CONSTANCES cohort;3C-Dijon Study;Cerba Health-Care;Etablissement du Sang study group;Anderson MS;Boisson B;Béziat V;Zhang SY;Vandreakos E;Hermine O;Pujol A;Peterson P;Mogensen TH;Rowen L;Mond J;Debette S;de Lamballerie X;Duval X;Mentré F;Zins M;Soler-Palacin P;Colobran R;Gorochov G;Solanich X;Susen S;Martinez-Picado J;Raoult D;Vasse M;Gregersen PK;Piemonti L;Rodríguez-Gallego C;Notarangelo LD;Su HC;Kisand K;Okada S;Puel A;Jouanguy E;Rice CM;Tiberghien P;Zhang Q;Cobat A;Abel L;Casanova JL
在10%的重症新冠肺炎肺炎患者中发现了中和高浓度干扰素-α和/或-ω的自身抗体，但在无症状感染的患者中未发现这种抗体。我们在3,595名新冠肺炎危重患者中的13.6%检测到中和低100倍的、更具生理性的干扰素-α和/或-ω(100pg/mL，1/10稀释度)的自身抗体，包括374名80岁患者中的21%和522名重症新冠肺炎患者中的6.5%。在1124名死亡患者中也有18%检测到这些抗体(年龄20天-99岁；平均70岁)。此外，另外1.3%的重症新冠肺炎患者和0.9%的死亡患者有中和高浓度干扰素-β的自身抗体。我们还显示，在34,159名普通人群中未感染的受试者样本中，18岁至69岁、70岁至79岁和80岁之间的人中有0.18%的人存在中和高浓度干扰素-α和/或-ω的自体抗体，而在80岁的人中有3.4%。此外，在10,778名未感染的人中，携带中和浓度较低的自动抗体的受试者比例更高：1%的人70岁，2.3%的人在70岁至80岁之间，6.3%的人在80岁。相比之下，中和干扰素-β的自动抗体并没有随着年龄的增长而变得更加频繁。自身抗体中和I型IFN早于SARS-CoV-2感染，并在70岁后患病率急剧上升。他们占80岁以上新冠肺炎危重病例和新冠肺炎死亡病例总数的20%左右。中和I型IFN的自身抗体在60岁以上的患病率增加，约占所有致命新冠肺炎病例的20%。
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases. Autoantibodies neutralizing type I IFNs increase in prevalence over 60 years of age and underlie about 20% of all fatal COVID-19 cases.
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DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
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
影响因子：
82.9
作者：
Brodin, Petter
通讯作者：
Brodin, Petter
影响因子：
2
作者：
Heinze, G;Schemper, M
通讯作者：
Schemper, M
影响因子：
1.8
作者：
Agresti, A;Coull, BA
通讯作者：
Coull, BA