Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

作者：Paul Bastard, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Jérémy Manry, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Shohei Eto, Marina García-Prat, Lucy Bizien, Alba Parra-Martínez, Rui Yang, Liis Haljasmägi, Mélanie Migaud, Karita Särekannu, Julia Maslovskaja, Nicolas de Prost, Yacine Tandjaoui-Lambiotte, Charles‐Édouard Luyt, Blanca Amador-Borrero, Alexandre Gaudet, Julien Poissy, Pascal Morel, Pascale Richard, Fabrice Cognasse, Jesús Troya, Sophie Trouillet‐Assant, Alexandre Bélot, Kahina Saker, Pierre Garçon, Jacques G. Rivière, Jean‐Christophe Lagier, Stéphanie Gentile, Lindsey B. Rosen, Elana R. Shaw, Tomohiro Morio, Junko Tanaka, David Dalmau, Pierre‐Louis Tharaux, D. Sène, Alain Stépanian, Bruno Mégarbane, Vasiliki Triantafyllia, Arnaud Fekkar, James R. Heath, José Luis Franco, Juan‐Manuel Anaya, Jordi Solé‐Violán, Luisa Imberti, Andrea Biondi, Paolo Bonfanti, Riccardo Castagnoli, Ottavia M. Delmonte, Yu Zhang, Andrew L. Snow, Steven M. Holland, Catherine M. Biggs, Marcela Moncada‐Vélez, Andrés Augusto Arias, Lazaro Lorenzo, Soraya Boucherit, Boubacar Coulibaly, Dany Anglicheau, Anna Maria Planas, Filomeen Haerynck, Sotiriјa Duvlis, Robert Luke Nussbaum, Tayfun Özçelık, Sevgi Keleş, Ahmed Aziz Bousfiha, Jalila El Bakkouri, Carolina Ramı́rez-Santana, Stéphane Paul, Qiang Pan‐Hammarström, Lennart L G Hammarström, Annabelle Dupont, Alina Kurolap, Christine Noel Metz, Alessandro Aiuti, Giorgio Casari, Vito Lampasona, Fabio Ciceri, Lucila Akune Barreiros, Elena Domínguez‐Garrido, Mateus Vidigal, Mayana Zatz, Diederik van de Beek, Sabina Sahanic, Ivan Tancevski, Yuriy Stepanovskyy, Oksana R. Boyarchuk, Yoko Nukui, Miyuki Tsumura, Loreto Vidaur, Stuart G. Tangye, Sonia Burrel, Darragh Duffy, Lluís Quintana‐Murci, Adam Klocperk, Nelli Y. Kann, Anna Shcherbina, YL Lau, Daniel Leung, Matthieu Coulongeat, Julien Marlet, Rutger Koning, Luis Felipe Reyes, Angélique Chauvineau‐Grenier, Fabienne Venet, Guillaume Monneret, Michel C. Nussenzweig, Romain Arrestier, Idris Boudhabhay, Hagit Baris Feldman, David Hagin, Joost Wauters, Isabelle Meyts, Adam H. Dyer, Seán Kennelly, Nollaig M. Bourke, Rabih Halwani, Narjes Saheb Sharif‐Askari, Karim Dorgham, Jérôme Sallette, Souad Mehlal Sedkaoui, Suzan A. AlKhater, Raul Francisco Rigo-Bonnin, Francisco Barreiro Morandeira, Lucie Roussel, Donald Cuong Vinh, Sisse Rye Ostrowski, Antônio Condino‐Neto, Carolina Prando, Anastasiia V. Bondarenko, András N. Spaan, Laurent Gilardin, Jacques Fellay, Stanislas Lyonnet, Kaya Bilgüvar, Richard P. Lifton, Shrikant Mane, HGID Lab, NIAID Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, French COVID Cohort Study Group, Imagine COVID-Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank Investigators, COVID Human Genetic Effort, CONSTANCES cohort, 3C-Dijon Study, Cerba HealthCare, Etablissement du Sang study group, Mark Stuart Anderson, Bertrand Boisson, Vivien Béziat, Shen‐Ying Zhang, Evangelos Andreakos, Olivier Hermine, Aurora Pujol, Pärt Peterson, Trine Hyrup Mogensen, Lee Rowen, James Mond, Stéphanie Debette, Xavier Nicolas de Lamballerie, Xavier Duval, France Mentré, Marie Zins, Pere Soler‐Palacín, Roger Colobrán, Guy Gorochov, Xavier Solanich, Sophie Susen, Javier Martínez‐Picado, Didier Raoult, Marc Vasse, Peter K. Gregersen, Lorenzo Piemonti, Carlos Rodríguez‐Gallego, Luigi Daniele Notarangelo, Helen C. Su, Kai E. Kisand, Satoshi Okada, Anne Puel, Emmanuelle Jouanguy, Charles M. Rice, Pierre Tiberghien, Qian Zhang, Aurélie Cobat, Laurent Abel, Jean‐Laurent Casanova · 发表于：Science Immunology · 年份：2021 · DOI：10.1126/sciimmunol.abl4340 · 被引用次数：643 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、Diabetes and associated disorders

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 individuals <70 years, 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 ...