Autoantibodies neutralizing type I IFNs are present in
Document Type
Article
Publication Date
8-19-2021
Publication Title
Sci Immunol
Keywords
washington; seattle; isb
Abstract
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individualsyears, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.
Department
Infectious Diseases
Department
Institute for Systems Biology
Recommended Citation
Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Rosain, Jérémie; Philippot, Quentin; Manry, Jérémy; Michailidis, Eleftherios; Hoffmann, Hans-Heinrich; Eto, Shohei; Garcia-Prat, Marina; Bizien, Lucy; Parra-Martínez, Alba; Yang, Rui; Haljasmägi, Liis; Migaud, Mélanie; Särekannu, Karita; Maslovskaja, Julia; de Prost, Nicolas; Tandjaoui-Lambiotte, Yacine; Luyt, Charles-Edouard; Amador-Borrero, Blanca; Gaudet, Alexandre; Poissy, Julien; Morel, Pascal; Richard, Pascale; Cognasse, Fabrice; Troya, Jesus; Trouillet-Assant, Sophie; Belot, Alexandre; Saker, Kahina; Garçon, Pierre; Rivière, Jacques G; Lagier, Jean-Christophe; Gentile, Stéphanie; Rosen, Lindsey B; Shaw, Elana; Morio, Tomohiro; Tanaka, Junko; Dalmau, David; Tharaux, Pierre-Louis; Sene, Damien; Stepanian, Alain; Megarbane, Bruno; Triantafyllia, Vasiliki; Fekkar, Arnaud; Heath, James R; Franco, José Luis; Anaya, Juan-Manuel; Solé-Violán, Jordi; Imberti, Luisa; Biondi, Andrea; Bonfanti, Paolo; Castagnoli, Riccardo; Delmonte, Ottavia M; Zhang, Yu; Snow, Andrew L; Holland, Steven M; Biggs, Catherine; Moncada-Vélez, Marcela; Arias, Andrés Augusto; Lorenzo, Lazaro; Boucherit, Soraya; Coulibaly, Boubacar; Anglicheau, Dany; Planas, Anna M; Haerynck, Filomeen; Duvlis, Sotirija; Nussbaum, Robert L; Ozcelik, Tayfun; Keles, Sevgi; Bousfiha, Ahmed A; El Bakkouri, Jalila; Ramirez-Santana, Carolina; Paul, Stéphane; Pan-Hammarström, Qiang; Hammarström, Lennart; Dupont, Annabelle; Kurolap, Alina; Metz, Christine N; Aiuti, Alessandro; Casari, Giorgio; Lampasona, Vito; Ciceri, Fabio; Barreiros, Lucila A; Dominguez-Garrido, Elena; Vidigal, Mateus; Zatz, Mayana; van de Beek, Diederik; Sahanic, Sabina; Tancevski, Ivan; Stepanovskyy, Yurii; Boyarchuk, Oksana; Nukui, Yoko; Tsumura, Miyuki; Vidaur, Loreto; Tangye, Stuart G; Burrel, Sonia; Duffy, Darragh; Quintana-Murci, Lluis; Klocperk, Adam; Kann, Nelli Y; Shcherbina, Anna; Lau, Yu-Lung; Leung, Daniel; Coulongeat, Matthieu; Marlet, Julien; Koning, Rutger; Reyes, Luis Felipe; Chauvineau-Grenier, Angélique; Venet, Fabienne; Monneret, Guillaume; Nussenzweig, Michel C; Arrestier, Romain; Boudhabhay, Idris; Baris-Feldman, Hagit; Hagin, David; Wauters, Joost; Meyts, Isabelle; Dyer, Adam H; Kennelly, Sean P; Bourke, Nollaig M; Halwani, Rabih; Sharif-Askari, Narjes Saheb; Dorgham, Karim; Sallette, Jérome; Sedkaoui, Souad Mehlal; AlKhater, Suzan; Rigo-Bonnin, Raúl; Morandeira, Francisco; Roussel, Lucie; Vinh, Donald C; Ostrowski, Sisse Rye; Condino-Neto, Antonio; Prando, Carolina; Bonradenko, Anastasiia; Spaan, András N; Gilardin, Laurent; Fellay, Jacques; Lyonnet, Stanislas; Bilguvar, Kaya; Lifton, Richard P; Mane, Shrikant; Lab, HGID; Clinicians, COVID; Clinicians, COVID-STORM; Response to COVID Group, NIAID Immune; Study Group, NH-COVAIR; CHGE, Danish; Donor Study, Danish Blood; Hospital, St. James's; Interest group, SARS CoV2; Cohort Study Group, French COVID; COVID-Group, Imagine; Consortium, Milieu Intérieur; Cohort, CoV-Contact; UMC Covid-19, Amsterdam; Investigators, Biobank; Human Genetic Effort, COVID; cohort, CONSTANCES; Study, 3C-Dijon; Health-Care, Cerba; du Sang study group, Etablissement; Anderson, Mark S; Boisson, Bertrand; Béziat, Vivien; Zhang, Shen-Ying; Vandreakos, Evangelos; Hermine, Olivier; Pujol, Aurora; Peterson, Pärt; Mogensen, Trine H; Rowen, Lee; Mond, James; Debette, Stéphanie; de Lamballerie, Xavier; Duval, Xavier; Mentré, France; Zins, Marie; Soler-Palacin, Pere; Colobran, Roger; Gorochov, Guy; Solanich, Xavier; Susen, Sophie; Martinez-Picado, Javier; Raoult, Didier; Vasse, Marc; Gregersen, Peter K; Piemonti, Lorenzo; Rodríguez-Gallego, Carlos; Notarangelo, Luigi D; Su, Helen C; Kisand, Kai; Okada, Satoshi; Puel, Anne; Jouanguy, Emmanuelle; Rice, Charles M; Tiberghien, Pierre; Zhang, Qian; Cobat, Aurélie; Abel, Laurent; and Casanova, Jean-Laurent, "Autoantibodies neutralizing type I IFNs are present in" (2021). Articles, Abstracts, and Reports. 5184.
https://digitalcommons.providence.org/publications/5184
