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

Identifier:  imarina:8681132

Handle: https://hdl.handle.net/20.500.11797/imarina8681132

Authors:  Bastard, Paul; Rosen, Lindsey B; Zhang, Qian; Michailidis, Eleftherios; Hoffmann, Hans-Heinrich; Zhang, Yu; Dorgham, Karim; Philippot, Quentin; Rosain, Jeremie; Beziat, Vivien; Manry, Jeremy; Shaw, Elana; Haljasmagi, Liis; Peterson, Part; Lorenzo, Lazaro; Bizien, Lucy; Trouillet-Assant, Sophie; Dobbs, Kerry; de Jesus, Adriana Almeida; Belot, Alexandre; Kallaste, Anne; Catherinot, Emilie; Tandjaoui-Lambiotte, Yacine; Le Pen, Jeremie; Kerner, Gaspard; Bigio, Benedetta; Seeleuthner, Yoann; Yang, Rui; Bolze, Alexandre; Spaan, Andras N; Delmonte, Ottavia M; Abers, Michael S; Aiuti, Alessandro; Casari, Giorgio; Lampasona, Vito; Piemonti, Lorenzo; Ciceri, Fabio; Bilguvar, Kaya; Lifton, Richard P; Vasse, Marc; Smadja, David M; Migaud, Melanie; Hadjadj, Jerome; Terrier, Benjamin; Duffy, Darragh; Quintana-Murci, Lluis; van de Beek, Diederik; Roussel, Lucie; Vinh, Donald C; Tangye, Stuart G; Haerynck, Filomeen; Dalmau, David; Martinez-Picado, Javier; Brodin, Petter; Nussenzweig, Michel C; Boisson-Dupuis, Stephanie; Rodriguez-Gallego, Carlos; Vogt, Guillaume; Mogensen, Trine H; Oler, Andrew J; Gu, Jingwen; Burbelo, Peter D; Cohen, Jeffrey I; Biondi, Andrea; Bettini, Laura Rachele; D'Angio, Mariella; Bonfanti, Paolo; Rossignol, Patrick; Mayaux, Julien; Rieux-Laucat, Frederic; Husebye, Eystein S; Fusco, Francesca; Ursini, Matilde Valeria; Imberti, Luisa; Sottini, Alessandra; Paghera, Simone; Quiros-Roldan, Eugenia; Rossi, Camillo; Castagnoli, Riccardo; Montagna, Daniela; Licari, Amelia; Marseglia, Gian Luigi; Duval, Xavier; Ghosn, Jade; Tsang, John S; Goldbach-Mansky, Raphaela; Kisand, Kai; Lionakis, Michail S; Puel, Anne; Zhang, Shen-Ying; Holland, Steven M; Gorochov, Guy; Jouanguy, Emmanuelle; Rice, Charles M; Cobat, Aurelie; Notarangelo, Luigi D; Abel, Laurent; Su, Helen C; Casano

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-omega (IFN-omega) (13 patients), against the 13 types of IFN-alpha (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 lifethreatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.