Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children.
Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children.
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DOI：
10.1084/jem.20231353
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发表时间：
2024-02-05
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在大约10%的COVID-19肺炎儿童中发现了中和IFN-α和/或IFN-ω的自身抗体。在未感染的儿童中，中和IFN-α2的自体抗体（0.2%）比中和IFN-ω的（2%）少。因此，针对IFN-α的自身抗体会增加COVID-19肺炎的风险。我们发现183例因COVID-19肺炎住院的未接种疫苗的儿童中有19例（10.4%）有自身抗体（auto-Abs）中和I型IFN（10例为IFN-α2, 3例为IFN-α2, 5例为IFN-α2 + IFN-ω， 2例为IFN-α2， IFN-ω + IFN-β， 9例为IFN-ω）。7名儿童（3.8%）的抗体中和至少10 ng/ml的一种IFN，而其他12名儿童（6.6%）的抗体中和仅100 pg/ml。自体抗体能中和未糖基化和糖基化的ifn。我们还在2,267名未感染儿童中检测到4名（0.2%）中和100 pg/ml IFN-α2的auto-Abs，在45名（2%）儿童中检测到中和IFN-ω的auto-Abs。因此，仅中和IFN-α2的auto-Abs治疗危及生命的COVID-19肺炎的优势比（OR [95% CI] = 67.6[5.7-9,196.6]）高于仅中和IFN-ω的auto-Abs （OR [95% CI] = 2.6[1.2-5.3]）。中和高浓度IFN-ω和/或IFN-α2的auto-Abs （OR [95% CI] = 12.9[4.6-35.9]）的OR也高于中和低浓度IFN-ω和/或IFN-α2的OR （OR [95% CI] = 5.5[3.1-9.6]）。
Auto-Abs neutralizing IFN-α and/or IFN-ω are found in about 10% of children with COVID-19 pneumonia. In uninfected children, auto-Abs neutralizing IFN-α2 are rarer (0.2%) than those neutralizing IFN-ω (2%). Auto-Abs against IFN-α thus confer a greater risk of COVID-19 pneumonia. We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2–5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6–35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1–9.6]) of IFN-ω and/or IFN-α2.
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DOI：
10.1126/science.abj7965
发表时间：
2021-11-26
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Casanova JL;Abel L
通讯作者：
Abel L
影响因子：
15.9
作者：
Casanova, Jean-Laurent;Anderson, Mark S.
通讯作者：
Anderson, Mark S.
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：
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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：
24.8
作者：
通讯作者：
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影响因子：
9.1
作者：
Akbil, Bengisu;Meyer, Tim;Stubbemann, Paula;Thibeault, Charlotte;Staudacher, Olga;Niemeyer, Daniela;Jansen, Jenny;Muehlemann, Barbara;Doehn, Jan;Tabeling, Christoph;Nusshag, Christian;Hirzel, Cedric;Sanchez, David Soekler;Nieters, Alexandra;Lother, Achim;Duerschmied, Daniel;Schallner, Nils;Lieberum, Jan Nikolaus;August, Dietrich;Rieg, Siegbert;Falcone, Valeria;Hengel, Hartmut;Koelsch, Uwe;Unterwalder, Nadine;Huebner, Ralf-Harto;Jones, Terry C.;Suttorp, Norbert;Drosten, Christian;Warnatz, Klaus;Spinetti, Thibaud;Schefold, Joerg C.;Doerner, Thomas;Sander, Leif Erik;Corman, Victor M.;Merle, Uta;Kurth, Florian;von Bernuth, Horst;Meisel, Christian;Goffinet, Christine
通讯作者：
Goffinet, Christine