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Journal Articles Science Year : 2020

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

Paul Bastard (1, 2) , Lindsey B. Rosen (3) , Qian Zhang (2) , Eleftherios Michailidis (2) , Hans-Heinrich Hoffmann (2) , Yu Zhang (3) , Karim Dorgham (4) , Quentin Philippot (1) , Jérémie Rosain (1) , Vivien Béziat (1, 2) , Jérémy Manry (1) , Elana Shaw (3) , Liis Haljasmägi (5) , Pärt Peterson (5) , Lazaro Lorenzo (1) , Lucy Bizien (1) , Sophie Trouillet-Assant (6, 7) , Kerry Dobbs (3) , Adriana Almeida de Jesus (3) , Alexandre Belot (7, 8, 9) , Anne Kallaste (10) , Emilie Catherinot (11) , Yacine Tandjaoui-Lambiotte (12, 13) , Jeremie Le Pen (2) , Gaspard Kerner (1) , Benedetta Bigio (2) , Yoann Seeleuthner (1) , Rui Yang (2) , Alexandre Bolze (14) , András N. Spaan (2, 15) , Ottavia M. Delmonte (3) , Michael S. Abers (3) , Alessandro Aiuti (16, 17) , Giorgio Casari (16, 17) , Vito Lampasona (16, 17) , Lorenzo Piemonti (16, 17) , Fabio Ciceri (16, 17) , Kaya Bilguvar (18) , Richard P. Lifton (18, 2) , Marc Vasse (11) , David Smadja (19) , Mélanie Migaud (1) , Jérome Hadjadj (20) , Benjamin Terrier (21, 22) , Darragh Duffy (23) , Lluis Quintana-Murci (24, 25) , Diederik van de Beek (26) , Lucie Roussel (27) , Donald C. Vinh (27) , Stuart G. Tangye (28, 29) , Filomeen Haerynck (30) , David Dalmau (31, 32) , Javier Martinez-Picado (33, 34, 35) , Petter Brodin (36, 37) , Michel C. Nussenzweig (2, 38) , Stéphanie Boisson-Dupuis (1, 2) , Carlos Rodríguez-Gallego (39, 40) , Guillaume Vogt (41) , Trine H. Mogensen (42, 43) , Andrew J. Oler (3) , Jingwen Gu (3) , Peter D. Burbelo (44) , Jeffrey Cohen (3) , Andrea Biondi (45, 46) , Laura Rachele Bettini (45, 46) , Mariella d'Angio (45, 46) , Paolo Bonfanti (47, 45) , Patrick Rossignol (48, 49, 50, 51) , Julien Mayaux (21) , Frédéric Rieux-Laucat (20) , Eystein S. Husebye (52, 53, 36) , Francesca Fusco (54) , Matilde Valeria Ursini (54) , Luisa Imberti (55) , Alessandra Sottini (55) , Simone Paghera (55) , Eugenia Quiros-Roldan (56, 55) , Camillo Rossi (55) , Riccardo Castagnoli (57, 58) , Daniela Montagna (58, 57) , Amelia Licari (57, 58) , Gian Luigi Marseglia (57, 58) , Xavier Duval (59, 60, 61, 62) , Jade Ghosn (61, 60) , John S. Tsang (3) , Raphaela Goldbach-Mansky (3) , Kai Kisand (5) , Michail S. Lionakis (3) , Anne Puel (1, 2) , Shen-Ying Zhang (1, 2) , Steven M. Holland (3) , Guy Gorochov (4, 21) , Emmanuelle Jouanguy (1, 2) , Charles M. Rice (2) , Aurélie Cobat (1, 2) , Luigi D. Notarangelo (3) , Laurent Abel (1) , Jean-Christophe Richard (63, 64) , Helen Su (3) , Jean-Laurent Casanova (1, 2, 38, 65) , Christelle Tual (66) , Yazdan Yazdanpanah (60) , Sylvie van Der Werf (67)
1 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
2 Rockefeller University [New York]
3 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]
4 CIMI - Centre d'Immunologie et des Maladies Infectieuses
5 University of Tartu
6 HCL - Hospices Civils de Lyon
7 CIRI - Centre International de Recherche en Infectiologie
8 RAISE - Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon]
9 LIFe - Lyon Immunopathology Federation
10 Tartu University Hospital [Tartu, Estonia]
11 Hôpital Foch [Suresnes]
12 Hôpital Avicenne [AP-HP]
13 H&P - U1272 Inserm - Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires
14 Helix [San Mateo, CA]
15 University Medical Center [Utrecht]
16 IRCCS Ospedale San Raffaele [Milan, Italy]
17 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
18 YSM - Yale School of Medicine [New Haven, Connecticut]
19 IThEM - U1140 - Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis
20 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
21 CHU Pitié-Salpêtrière [AP-HP]
22 UPCité - Université Paris Cité
23 Immunologie Translationnelle - Translational Immunology lab
24 Génétique Evolutive Humaine - Human Evolutionary Genetics
25 Collège de France - Chaire Génomique humaine et évolution
26 Amsterdam Neuroscience [Pays-Bas]
27 MUHC - McGill University Health Center [Montreal]
28 Garvan Institute of medical research
29 UNSW - University of New South Wales [Sydney]
30 Ghent University Hospital
31 Hospital Universitario Mutua de Terrassa
32 UB - Universitat de Barcelona
33 IGTP - Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute
34 Universitat de Vic-Universitat Central de Catalunya, España
35 ICREA - Institució Catalana de Recerca i Estudis Avançats
36 Karolinska Institutet [Stockholm]
37 Karolinska University Hospital [Stockholm]
38 HHMI - Howard Hughes Medical Institute [New York]
39 Hospital Universitario de Gran Canaria Dr Negrin
40 University Fernando Pessoa - UFP
41 CNRGH - Centre National de Recherche en Génomique Humaine
42 Aarhus University Hospital
43 Aarhus University [Aarhus]
44 NIH - National Institutes of Health [Bethesda, MD, USA]
45 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
46 Fondazione MBBM-Ospedale [Monza, Italie]
47 San Gerardo Hospital of Monza
48 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
49 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
50 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
51 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
52 UiB - University of Bergen
53 Haukeland University Hospital
54 CNR - Consiglio Nazionale delle Ricerche [Napoli]
55 Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia]
56 UniBs - Università degli Studi di Brescia = University of Brescia
57 UNIPV - Università degli Studi di Pavia = University of Pavia
58 Fondazione IRCCS Policlinico San Matteo
59 CIC - CHU Bichat
60 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
61 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
62 UFR Médecine UPCité - UFR Médecine [Santé] - Université Paris Cité
63 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
64 MYRIAD - Modeling & analysis for medical imaging and Diagnosis
65 Service d'immuno-hématologie pédiatrique [CHU Necker]
66 CIC - Centre d'Investigation Clinique [Rennes]
67 CNRS-UMR3569 - Virologie
Qian Zhang
Liis Haljasmägi
Pärt Peterson
Benedetta Bigio
Rui Yang
Alexandre Bolze
Diederik van de Beek
Filomeen Haerynck
Kai Kisand
Sylvie van Der Werf

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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pasteur-02958871 , version 1 (06-10-2020)

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Paul Bastard, Lindsey B. Rosen, Qian Zhang, Eleftherios Michailidis, Hans-Heinrich Hoffmann, et al.. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science, 2020, 370 (6515), pp.eabd4585. ⟨10.1126/science.abd4585⟩. ⟨pasteur-02958871⟩
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