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

Paul Bastard Lindsey Rosen Qian Zhang Eleftherios Michailidis Hans-Heinrich Hoffmann Yu Zhang Karim Dorgham Quentin Philippot Jérémie Rosain Vivien Béziat Jérémy Manry Elana Shaw Liis Haljasmägi Pärt Peterson Lazaro Lorenzo Lucy Bizien Sophie Trouillet-Assant Kerry Dobbs Adriana Almeida de Jesus Alexandre Belot Anne Kallaste Emilie Catherinot Yacine Tandjaoui-Lambiotte Jeremie Le Pen Gaspard Kerner Benedetta Bigio Yoann Seeleuthner Rui Yang Alexandre Bolze András Spaan Ottavia Delmonte Michael Abers Alessandro Aiuti Giorgio Casari Vito Lampasona Lorenzo Piemonti Fabio Ciceri Kaya Bilguvar Richard Lifton Marc Vasse David Smadja Mélanie Migaud Jérome Hadjadj Benjamin Terrier Darragh Duffy 1 Lluis Quintana-Murci 2 Diederik van de Beek Lucie Roussel Donald Vinh Stuart Tangye Filomeen Haerynck David Dalmau Javier Martinez-Picado Petter Brodin Michel Nussenzweig Stéphanie Boisson-Dupuis Carlos Rodríguez-Gallego Guillaume Vogt Trine Mogensen Andrew Oler Jingwen Gu Peter Burbelo Jeffrey Cohen Andrea Biondi Laura Rachele Bettini Mariella d'Angio Paolo Bonfanti Patrick Rossignol Julien Mayaux Frédéric Rieux-Laucat Eystein Husebye Francesca Fusco Matilde Valeria Ursini Luisa Imberti Alessandra Sottini Simone Paghera Eugenia Quiros-Roldan Camillo Rossi Riccardo Castagnoli Daniela Montagna Amelia Licari Gian Luigi Marseglia Xavier Duval Jade Ghosn John Tsang Raphaela Goldbach-Mansky Kai Kisand Michail Lionakis Anne Puel Shen-Ying Zhang Steven Holland Guy Gorochov Emmanuelle Jouanguy Charles Rice Aurélie Cobat Luigi Notarangelo Laurent Abel Helen Su Jean-Laurent Casanova
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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03263254
Contributor : Laurence Langlais <>
Submitted on : Thursday, June 17, 2021 - 10:28:35 AM
Last modification on : Friday, July 9, 2021 - 11:18:04 AM

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Distributed under a Creative Commons Attribution 4.0 International License

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Paul Bastard, Lindsey Rosen, Qian Zhang, Eleftherios Michailidis, Hans-Heinrich Hoffmann, et al.. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science, American Association for the Advancement of Science, 2020, 370 (6515), pp.eabd4585. ⟨10.1126/science.abd4585⟩. ⟨pasteur-03263254⟩

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