Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or 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 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
Auto-antibodies against type I IFNs in patients with life-threatening COVID-19 / Bastard, Paul; Rosen, Lindsey B; Zhang, Qian; Michailidis, Eleftherios; Hoffmann, Hans-Heinrich; Zhang, Yu; Dorgham, Karim; Philippot, Quentin; Rosain, Jérémie; Béziat, Vivien; Manry, Jérémy; Shaw, Elana; Haljasmägi, Liis; Peterson, Pärt; 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, András 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, Mélanie; Hadjadj, Jérome; 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, Stéphanie; Rodríguez-Gallego, Carlos; Vogt, Guillaume; Mogensen, Trine H; Oler, Andrew J; Gu, Jingwen; Burbelo, Peter D; Cohen, Jeffrey; Biondi, Andrea; Bettini, Laura Rachele; D'Angio, Mariella; Bonfanti, Paolo; Rossignol, Patrick; Mayaux, Julien; Rieux-Laucat, Frédéric; 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, Aurélie; Notarangelo, Luigi D; Abel, Laurent; Su, Helen C; Casanova, Jean-Laurent. - In: SCIENCE. - ISSN 0036-8075. - (2020), p. eabd4585. [Epub ahead of print] [10.1126/science.abd4585]
Auto-antibodies against type I IFNs in patients with life-threatening COVID-19
Aiuti, Alessandro;Casari, Giorgio;Piemonti, Lorenzo;Ciceri, Fabio;
2020-01-01
Abstract
Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or 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 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
