Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals…

Published: 2021-08-10
Venue: Science Immunology, vol. 6, no. 62
Cited by: 608
Open access: Yes, hybrid
DOI: 10.1126/sciimmunol.abl4340
PubMed: 34413139

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 individuals 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.

Abstract

@article{bastard2021autoantibodies, title = {{Autoantibodies neutralizing type I IFNs are present in ~4\% of uninfected individuals over 70 years old and account for ~20\% of COVID-19 deaths}}, author = {Paul Bastard and Adrian Gervais and Tom Le Voyer and Jérémie Rosain and Quentin Philippot and Jérémy Manry and Eleftherios Michailidis and Hans-Heinrich Hoffmann and Shohei Eto and Marina García-Prat and Lucy Bizien and Alba Parra-Martínez and Rui Yang and Liis Haljasmägi and Mélanie Migaud and Karita Särekannu and Julia Maslovskaja and Nicolas de Prost and Yacine Tandjaoui-Lambiotte and Charles Edouard Luyt and Blanca Amador-Borrero and Alexandre Gaudet and Julien Poissy and Pascal Morel and Pascale Richard and Fabrice Cognasse and Jesús Troya and Sophie Trouillet‐Assant and Alexandre Bélot and Kahina Saker and Pierre Garçon and Jacques Gabriel Riviere and Jean‐Christophe Lagier and Stéphanie Gentile and Lindsey B. Rosen and Elana R. Shaw and Tomohiro Morio and Junko Tanaka and David Dalmau and Pierre‐Louis Tharaux and D. Sène and Alain Stépanian and Bruno Mégarbane and Vasiliki Triantafyllia and Arnaud Fekkar and James R. Heath and José Luis Franco and Juan‐Manuel Anaya and Jordi Solé‐Violán and Luisa Imberti and Andrea Biondi and Paolo Bonfanti and Riccardo Castagnoli and Ottavia M. Delmonte and Yu Zhang and Andrew L. Snow and Steven M. Holland and Catherine M. Biggs and Marcela Moncada‐Vélez and Andrés Augusto Arias and Lazaro Lorenzo and Soraya Boucherit and Boubacar Coulibaly and Dany Anglicheau and Anna Maria Planas and Filomeen Haerynck and Sotiriјa Duvlis and Robert Luke Nussbaum and Tayfun Özçelık and Sevgi Keleş and Ahmed Aziz Bousfiha and Jalila El Bakkouri and Carolina Ramı́rez-Santana and Stéphane Paul and Qiang Pan‐Hammarström and Lennart L G Hammarström and Annabelle Dupont and Alina Kurolap and Christine Noel Metz and Alessandro Aiuti and Giorgio Casari and Vito Lampasona and Fabio Ciceri and Lucila Akune Barreiros and Elena Domínguez‐Garrido and Mateus Vidigal and Mayana Zatz and Diederik van de Beek and Sabina Sahanic and Ivan Tancevski and Yuriy Stepanovskyy and Oksana R. Boyarchuk and Yoko Nukui and Miyuki Tsumura and Loreto Vidaur and Stuart G. Tangye and Sonia Burrel and Darragh Duffy and Lluís Quintana‐Murci and Adam Klocperk and Nelli Y. Kann and Anna Yu. Shcherbina and YL Lau and Daniel Leung and Matthieu Coulongeat and Julien Marlet and Rutger Koning and Luis Felipe Reyes and Angélique Chauvineau‐Grenier and Fabienne Venet and Guillaume Monneret and Michel C. Nussenzweig and Romain Arrestier and Idris Boudhabhay and Hagit Baris Feldman and David Hagin and Joost Wauters and Isabelle Meyts and Adam H. Dyer and Seán Kennelly and Nollaig M. Bourke and Rabih Halwani and Narjes Saheb Sharif‐Askari and Karim Dorgham and Jérôme Sallette and Souad Mehlal and Suzan A. AlKhater and Raul Francisco Rigo-Bonnin and Francisco Morandeira and Lucie Roussel and Donald Cuong Vinh and Sisse Rye Ostrowski and Antônio Condino‐Neto and Carolina Prando and Anastasiia V. Bondarenko and András N. Spaan and Laurent Gilardin and Jacques Fellay and Stanislas Lyonnet and Kaya Bilgüvar and Richard P. Lifton and Shrikant Mane and HGID Lab and NIAID Immune Response to COVID Group and NH-COVAIR Study Group and Danish CHGE and Danish Blood Donor Study and French COVID Cohort Study Group and Imagine COVID-Group and CoV-Contact Cohort and Amsterdam UMC Covid-19 Biobank Investigators and COVID Human Genetic Effort and CONSTANCES cohort and 3C-Dijon Study and Cerba HealthCare and Etablissement du Sang study group and Mark Stuart Anderson and Bertrand Boisson and Vivien Béziat and Shen‐Ying Zhang and Evangelos Andreakos and Olivier Hermine and Aurora Pujol and Pärt Peterson and Trine Hyrup Mogensen and Lee Rowen and James Mond and Stéphanie Debette and Xavier Nicolas de Lamballerie and Xavier Duval and France Mentré and Marie Zins and Pere Soler‐Palacín and Roger Colobrán and Guy Gorochov and Xavier Solanich and Sophie Susen and Javier Martínez‐Picado and Didier Raoult and Marc Vasse and Peter K. Gregersen and Lorenzo Piemonti and Carlos Rodríguez‐Gallego and Luigi Daniele Notarangelo and Helen C. Su and Kai E. Kisand and Satoshi Okada and Anne Puel and Emmanuelle Jouanguy and Charles M. Rice and Pierre Tiberghien and Qian Zhang and Aurélie Cobat and Laurent Abel and Jean‐Laurent Casanova}, journal = {Science Immunology}, year = {2021}, volume = {6}, number = {62}, doi = {10.1126/sciimmunol.abl4340}, url = {https://doi.org/10.1126/sciimmunol.abl4340} }

TY - JOUR AU - Bastard, Paul AU - Gervais, Adrian AU - Voyer, Tom Le AU - Rosain, Jérémie AU - Philippot, Quentin AU - Manry, Jérémy AU - Michailidis, Eleftherios AU - Hoffmann, Hans-Heinrich AU - Eto, Shohei AU - García-Prat, Marina AU - Bizien, Lucy AU - Parra-Martínez, Alba AU - Yang, Rui AU - Haljasmägi, Liis AU - Migaud, Mélanie AU - Särekannu, Karita AU - Maslovskaja, Julia AU - Prost, Nicolas de AU - Tandjaoui-Lambiotte, Yacine AU - Luyt, Charles Edouard AU - Amador-Borrero, Blanca AU - Gaudet, Alexandre AU - Poissy, Julien AU - Morel, Pascal AU - Richard, Pascale AU - Cognasse, Fabrice AU - Troya, Jesús AU - Trouillet‐Assant, Sophie AU - Bélot, Alexandre AU - Saker, Kahina AU - Garçon, Pierre AU - Riviere, Jacques Gabriel AU - Lagier, Jean‐Christophe AU - Gentile, Stéphanie AU - Rosen, Lindsey B. AU - Shaw, Elana R. AU - Morio, Tomohiro AU - Tanaka, Junko AU - Dalmau, David AU - Tharaux, Pierre‐Louis AU - Sène, D. AU - Stépanian, Alain AU - Mégarbane, Bruno AU - Triantafyllia, Vasiliki AU - Fekkar, Arnaud AU - Heath, James R. AU - Franco, José Luis AU - Anaya, Juan‐Manuel AU - Solé‐Violán, Jordi AU - Imberti, Luisa AU - Biondi, Andrea AU - Bonfanti, Paolo AU - Castagnoli, Riccardo AU - Delmonte, Ottavia M. AU - Zhang, Yu AU - Snow, Andrew L. AU - Holland, Steven M. AU - Biggs, Catherine M. AU - Moncada‐Vélez, Marcela AU - Arias, Andrés Augusto AU - Lorenzo, Lazaro AU - Boucherit, Soraya AU - Coulibaly, Boubacar AU - Anglicheau, Dany AU - Planas, Anna Maria AU - Haerynck, Filomeen AU - Duvlis, Sotiriјa AU - Nussbaum, Robert Luke AU - Özçelık, Tayfun AU - Keleş, Sevgi AU - Bousfiha, Ahmed Aziz AU - Bakkouri, Jalila El AU - Ramı́rez-Santana, Carolina AU - Paul, Stéphane AU - Pan‐Hammarström, Qiang AU - Hammarström, Lennart L G AU - Dupont, Annabelle AU - Kurolap, Alina AU - Metz, Christine Noel AU - Aiuti, Alessandro AU - Casari, Giorgio AU - Lampasona, Vito AU - Ciceri, Fabio AU - Barreiros, Lucila Akune AU - Domínguez‐Garrido, Elena AU - Vidigal, Mateus AU - Zatz, Mayana AU - Beek, Diederik van de AU - Sahanic, Sabina AU - Tancevski, Ivan AU - Stepanovskyy, Yuriy AU - Boyarchuk, Oksana R. AU - Nukui, Yoko AU - Tsumura, Miyuki AU - Vidaur, Loreto AU - Tangye, Stuart G. AU - Burrel, Sonia AU - Duffy, Darragh AU - Quintana‐Murci, Lluís AU - Klocperk, Adam AU - Kann, Nelli Y. AU - Shcherbina, Anna Yu. AU - Lau, YL AU - Leung, Daniel AU - Coulongeat, Matthieu AU - Marlet, Julien AU - Koning, Rutger AU - Reyes, Luis Felipe AU - Chauvineau‐Grenier, Angélique AU - Venet, Fabienne AU - Monneret, Guillaume AU - Nussenzweig, Michel C. AU - Arrestier, Romain AU - Boudhabhay, Idris AU - Feldman, Hagit Baris AU - Hagin, David AU - Wauters, Joost AU - Meyts, Isabelle AU - Dyer, Adam H. AU - Kennelly, Seán AU - Bourke, Nollaig M. AU - Halwani, Rabih AU - Sharif‐Askari, Narjes Saheb AU - Dorgham, Karim AU - Sallette, Jérôme AU - Mehlal, Souad AU - AlKhater, Suzan A. AU - Rigo-Bonnin, Raul Francisco AU - Morandeira, Francisco AU - Roussel, Lucie AU - Vinh, Donald Cuong AU - Ostrowski, Sisse Rye AU - Condino‐Neto, Antônio AU - Prando, Carolina AU - Bondarenko, Anastasiia V. AU - Spaan, András N. AU - Gilardin, Laurent AU - Fellay, Jacques AU - Lyonnet, Stanislas AU - Bilgüvar, Kaya AU - Lifton, Richard P. AU - Mane, Shrikant AU - Lab, HGID AU - NIAID Immune Response to COVID Group AU - NH-COVAIR Study Group AU - CHGE, Danish AU - Study, Danish Blood Donor AU - French COVID Cohort Study Group AU - Imagine COVID-Group AU - Cohort, CoV-Contact AU - Investigators, Amsterdam UMC Covid-19 Biobank AU - Effort, COVID Human Genetic AU - cohort, CONSTANCES AU - Study, 3C-Dijon AU - HealthCare, Cerba AU - Etablissement du Sang study group AU - Anderson, Mark Stuart AU - Boisson, Bertrand AU - Béziat, Vivien AU - Zhang, Shen‐Ying AU - Andreakos, Evangelos AU - Hermine, Olivier AU - Pujol, Aurora AU - Peterson, Pärt AU - Mogensen, Trine Hyrup AU - Rowen, Lee AU - Mond, James AU - Debette, Stéphanie AU - Lamballerie, Xavier Nicolas de AU - Duval, Xavier AU - Mentré, France AU - Zins, Marie AU - Soler‐Palacín, Pere AU - Colobrán, Roger AU - Gorochov, Guy AU - Solanich, Xavier AU - Susen, Sophie AU - Martínez‐Picado, Javier AU - Raoult, Didier AU - Vasse, Marc AU - Gregersen, Peter K. AU - Piemonti, Lorenzo AU - Rodríguez‐Gallego, Carlos AU - Notarangelo, Luigi Daniele AU - Su, Helen C. AU - Kisand, Kai E. AU - Okada, Satoshi AU - Puel, Anne AU - Jouanguy, Emmanuelle AU - Rice, Charles M. AU - Tiberghien, Pierre AU - Zhang, Qian AU - Cobat, Aurélie AU - Abel, Laurent AU - Casanova, Jean‐Laurent TI - Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths JO - Science Immunology VL - 6 IS - 62 PY - 2021 DA - 2021/08/10 DO - 10.1126/sciimmunol.abl4340 UR - https://doi.org/10.1126/sciimmunol.abl4340 ER -

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

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

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