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Autoantibodies against type I IFNs in patients with critical influenza pneumonia

2022; Rockefeller University Press; Volume: 219; Issue: 11 Linguagem: Inglês

10.1084/jem.20220514

1540-9538

Qian Zhang, Andrés Pizzorno, Lisa Miorin, Paul Bastard, Adrian Gervais, Tom Le Voyer, Lucy Bizien, Jérémy Manry, Jérémie Rosain, Quentin Philippot, Kelian Goavec, Blandine Padey, Anastasija Čupić, Emilie Laurent, Kahina Saker, Martti Vanker, Karita Särekannu, Laurent Abel, Alessandro Aiuti, Saleh Al‐Muhsen, Fahd Al‐Mulla, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Hagit Baris Feldman, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed Aziz Bousfiha, Petter Brodin, Yenan T. Bryceson, Carlos D. Bustamante, Manish J. Butte, Giorgio Casari, John Christodoulou, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Murkesh Desai, Beth A. Drolet, Jamila El Baghdadi, Sara Elva Espinosa‐Padilla, Jacques Fellay, Carlos Flores, Paraskevi C. Fragkou, José Luis Barrera Franco, Antoine Froidure, Ioanna E. Galani, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Sarah E. Henrickson, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Erich D. Jarvis, Timokratis Karamitros, Kai Kisand, Ourania Koltsida, Cheng‐Lung Ku, Yu-Lung Lau, Yun Ling, C. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona OʼFarrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Özçelık, Qiang Pan‐Hammarström, Jean W. Pape, Rebeca Pérez de Diego, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Vasiliki Rapti, Laurent Rénia, Igor Resnick, Carlos Rodríguez‐Gallego, Νikoletta Ρovina, Vanessa Sancho‐Shimizu, Anna Šedivá, Mikko Seppänen, Mohammed Shahrooei, Anna Shcherbina, Ondřej Slabý, Andrew L. Snow, Pere Soler‐Palacín, András N. Spaan, Ivan Tancevski, Stuart G. Tangye, Ahmad Abou Tayoun, Şehime Gülsün Temel, Sotirios Tsiodras, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Paweł Zawadzki, Helen C. Su, Jean‐Laurent Casanova, Pascal Morel, Pascale Richard, Brigitte Bonneaudeau, Dorothée Cannet, Pierre Gallian, Michel Jeanne, Magali Perroquin, Hind Hamzeh‐Cognasse, Fabrice Cognasse, Pierre Tiberghien, Rachel Nadif, Marcel Goldberg, Anna Ozguler, Joseph Henny, Sylvie Lemonnier, Mireille Cœuret-Pellicer, Stéphane Le Got, Marie Zins, Christophe Tzourio, Stéphanie Debette, Carole Dufouil, Aïcha Soumaré, Morgane Lachaize, Nathalie Fievet, Amandine Flaig, Fernando Martin, Souad Mehlal-Sedkaoui, Jérôme Sallette, Romain Hernu, Bruno Lina, Carole Schwebel, I. Wroblewski, Patrice Morand, Bertrand Souweine, Benoît Bœuf, H. Peigue‐Lafeuille, Michaël Darmon, Hugues Patural, Bruno Pozzetto, Jean‐Pierre Quenot, Benoit Colomb, Pierre Pothier, Alexandre Bélot, María Abad Arranz, Manuela Aguilar Guisado, Ana Escoresca Ortega, Rafaela Ríos, Laura Merino Díaz, Maria Del Mar Muñoz Garcia, Nieves Ramírez Duque, Gloria María Romero Vázquez, Maria Jose Sánchez Cordero, Celia Salamanca Rivera, Jordí Niubó, Alexander Rombauts, Nicolás Navarrete, Laura Romero Oraa, Virginia Palomo, Tamara García‐Salum, Marcela Ferrés, Nicole Le Corre, Javier Sánchez‐Céspedes, María Balsera-Manzanero, Jordi Carratalà, Pilar Retamar, Gabriela Abelenda-Alonso, Adoración Valiente, Pierre Tiberghien, Marie Zins, Stéphanie Debette, Isabelle Meyts, Filomeen Haerynck, Riccardo Castagnoli, Luigi D. Notarangelo, Luis Ignacio González‐Granado, Nerea Domínguez‐Pinilla, Evangelos Andreakos, Vasiliki Triantafyllia, Carlos Rodríguez‐Gallego, Jordi Solé‐Violán, J.J. Ruiz-Hernández, Felipè Rodríguez de Castro, José Ferreres, M. Luisa Briones, Joost Wauters, Lore Vanderbeke, Simon Feys, Chen-Yen Kuo, Wei‐Te Lei, Cheng‐Lung Ku, Galit Tal, A Etzioni, Suhair Hanna, Thomas Fournet, Jean‐Sébastien Casalegno, Grégory Quéromès, Laurent Argaud, Étienne Javouhey, Manuel Rosa‐Calatrava, Elisa Cordero, Teresa Aydillo, Rafael Medina, Kai Kisand, Anne Puel, Emmanuelle Jouanguy, Laurent Abel, Aurelié Cobat, Sophie Trouillet‐Assant, Adolfo García‐Sastre, Jean‐Laurent Casanova,

Diabetes and associated disorders

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6–73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients’ autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10−5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10−5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10−10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.