Autoantibodies against type I IFNs in patients with life-threatening COVID-19
Publication date
2020-10-23
Authors
Bastard, Paul
Rosen, Lindsey B
Zhang, Qian
Michailidis, Eleftherios
Hoffmann, Hans-Heinrich
Zhang, Yu
Dorgham, Karim
Philippot, Quentin
Rosain, Jérémie
Béziat, Vivien
Editors
Advisors
Supervisors
Document Type
Article
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cc_by
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-w (IFN-w) (13 patients), against the 13 types of IFN-a (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.
Keywords
Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing/blood, Asymptomatic Infections, Autoantibodies/blood, Betacoronavirus, COVID-19, Case-Control Studies, Coronavirus Infections/immunology, Critical Illness, Female, Humans, Immunoglobulin G/blood, Interferon Type I/immunology, Interferon alpha-2/immunology, Male, Middle Aged, Pandemics, Pneumonia, Viral/immunology, SARS-CoV-2, General, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural, Journal Article, Research Support, N.I.H., Extramural
Citation
Bastard, P, Rosen, L B, Zhang, Q, Michailidis, E, Hoffmann, H-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 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 N, Delmonte, O M, Abers, M S, Aiuti, A, Casari, G, Lampasona, V, Piemonti, L, Ciceri, F, Bilguvar, K, Lifton, R P, Vasse, M, Smadja, D M, Migaud, M, Hadjadj, J, Terrier, B, Duffy, D, Quintana-Murci, L, van de Beek, D, Roussel, L, Vinh, D C, Tangye, S G, HGID Lab & Bruijning-Verhagen, P 2020, 'Autoantibodies against type I IFNs in patients with life-threatening COVID-19', Science, vol. 370, no. 6515, eabd4585. https://doi.org/10.1126/science.abd4585