Autoantibodies against type I IFNs in patients with life-threatening COVID-19.

Bastard P,Rosen L,Zhang Q,Michailidis E,Hoffmann H,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 A,Belot A,Kallaste A,Catherinot E,Tandjaoui-Lambiotte Y,Le Pen J,Kerner G,Bigio B,Seeleuthner Y,Yang R,Bolze A,Spaan A,Delmonte O,Abers M,Aiuti A,Casari G,Lampasona V,Piemonti L,Ciceri F,Bilguvar K,Lifton R,Vasse M,Smadja D,Migaud M,Hadjadj J,Terrier B,Duffy D,Quintana-Murci L,van de Beek D,Roussel L,Vinh D,Tangye S,Haerynck F,Dalmau D,Martinez-Picado J,Brodin P,Nussenzweig M,Boisson-Dupuis S,Rodríguez-Gallego C,Vogt G,Mogensen T,Oler A,Gu J,Burbelo P,Cohen J,Biondi A,Bettini L,D'Angio M,Bonfanti P,Rossignol P,Mayaux J,Rieux-Laucat F,Husebye E,Fusco F,Ursini M,Imberti L,Sottini A,Paghera S,Quiros-Roldan E,Rossi C,Castagnoli R,Montagna D,Licari A,Marseglia G,Duval X,Ghosn J,Tsang J,Goldbach-Mansky R,Kisand K,Lionakis M,Puel A,Zhang S,Holland S,Gorochov G,Jouanguy E,Rice C,Cobat A,Notarangelo L,Abel L,Su H,Casanova J

Source :

Science

2020 Sep 24

Pmid / DOI:

32972996

Abstract

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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