Autoantibodies against type I IFNs in patients with critical influenza pneumonia
Authors: Zhang Qian , Pizzorno Andrés , Miorin Lisa , Bastard Paul , Gervais Adrian , Le Voyer Tom , Bizien Lucy , Manry Jeremy , Rosain Jérémie , Philippot Quentin , Goavec Kelian , Padey Blandine , Cupic Anastasija , Laurent Emilie , Saker Kahina , Vanker Martti , Särekannu Karita ,   COVID Human Genetic Effort, Abel Laurent , Aiuti Alessandro , Al-Muhsen Saleh , Al-Mulla Fahd , Anderson Mark S. , Andreakos Evangelos , Arias Andrés A. , Baris Feldman Hagit , Belot Alexandre , Biggs Catherine M. , Bogunovic Dusan , Bolze Alexandre , Bondarenko Anastasiia , Bousfiha Ahmed A. , Brodin Petter , Bryceson Yenan , Bustamante Carlos D. , Butte Manish J. , Casari Giorgio , Christodoulou John , Condino-Neto Antonio , Constantinescu Stefan N. , Cooper Megan A. , Dalgard Clifton L. , Desai Murkesh , Drolet Beth A. , El Baghdadi Jamila , Espinosa-Padilla Sara , Fellay Jacques , Flores Carlos , Fragkou Paraskevi C. , Franco José Luis , Froidure Antoine , Galani Ioanna Evdokia , Gregersen Peter K. , Grimbacher Bodo , Haerynck Filomeen , Hagin David , Halwani Rabih , Hammarström Lennart , Heath James R. , Henrickson Sarah E. , Hsieh Elena W.Y. , Husebye Eystein , Imai Kohsuke , Itan Yuval , Jarvis Erich D. , Karamitros Timokratis , Kisand Kai , Koltsida Ourania , Ku Cheng-Lung , Lau Yu-Lung , Ling Yun , Lucas Carrie L. , Maniatis Tom , Mansouri Davood , Maródi László , Meyts Isabelle , Milner Joshua D. , Mironska Kristina , Mogensen Trine H. , Morio Tomohiro , Ng Lisa F.P. , Notarangelo Luigi D. , Novelli Antonio , Novelli Giuseppe , O'Farrelly Cliona , Okada Satoshi , Okamoto Keisuke , Ozcelik Tayfun , Pan-Hammarström Qiang , Pape Jean W. , Perez de Diego Rebeca , Perlin David S. , Pesole Graziano , Planas Anna M. , Prando Carolina , Pujol Aurora , Quintana-Murci Lluis , Ramaswamy Sathishkumar , Rapti Vasiliki , Renia Laurent , Resnick Igor , Rodríguez-Gallego Carlos , Rovina Nikoletta , Sancho-Shimizu Vanessa , Sediva Anna , Seppänen Mikko R.J. , Shahrooei Mohammed , Shcherbina Anna , Slaby Ondrej , Snow Andrew L. , Soler-Palacín Pere , Spaan András N. , Tancevski Ivan , Tangye Stuart G. , Abou Tayoun Ahmad , Temel Şehime Gülsün , Tsiodras Sotirios , Turvey Stuart E. , Uddin K.M. Furkan , Uddin Mohammed J. , van de Beek Diederik , Vinh Donald C. , von Bernuth Horst , Wauters Joost , Zatz Mayana , Zawadzki Pawel , Su Helen C. , Casanova Jean-Laurent ,   Etablissement Français du Sang Study Group, Morel Pascal , Richard Pascale , Bonneaudeau Brigitte , Cannet Dorothée , Gallian Pierre , Jeanne Michel , Perroquin Magali , Hamzeh-Cognasse Hind , Cognasse Fabrice , Tiberghien Pierre ,   Constances Cohort, Nadif Rachel , Goldberg Marcel , Ozguler Anna , Henny Joseph , Lemonnier Sylvie , Coeuret-Pellicer Mireille , Le Got Stéphane , Zins Marie ,   3C-Dijon Study, Tzourio Christophe , Debette Stéphanie , Dufouil Carole , Soumaré Aïcha , Lachaize Morgane , Fievet Nathalie , Flaig Amandine ,   Cerba HealthCare Group, Martin Fernando , Mehlal-Sedkaoui Souad , Sallette Jérôme ,   Lyon Antigrippe Working Group, Hernu Romain , Lina Bruno , Schwebel Carole , Wroblewski Isabelle , Morand Patrice , Souweine Bertrand , Boeuf Benoit , Peigue-Lafeuille Helene , Darmon Michael , Patural Hugues , Pozzetto Bruno , Quenot Jean Pierre , Colomb Benoit , Pothier Pierre , Belot Alexandre ,   REIPI INF Working Group, Abad Arranz Maria , Aguilar Guisado Manuela , Escoresca Ortega Ana , Gallardo Ríos Rafaela , Merino Díaz Laura , Del Mar Muñoz Garcia Maria , Ramírez Duque Nieves , Romero Vázquez Gloria María , Sánchez Cordero Maria Jose , Salamanca Rivera Celia , Niubó Jordi , Rombauts Alexander , Navarrete Nicolás , Romero Oraa Laura , Palomo Virginia , García-Salum Tamara , Ferres Marcela , Le Corre Nicole , Sánchez-Céspedes Javier , Balsera-Manzanero María , Carratala Jordi , Retamar-Gentil Pilar , Abelenda-Alonso Gabriela , Valiente Adoración , Tiberghien Pierre , Zins Marie , Debette Stéphanie , Meyts Isabelle , Haerynck Filomeen , Castagnoli Riccardo , Notarangelo Luigi D. , Gonzalez-Granado Luis I. , Dominguez-Pinilla Nerea , Andreakos Evangelos , Triantafyllia Vasiliki , Rodríguez-Gallego Carlos , Solé-Violán Jordi , Ruiz-Hernandez José Juan , Rodríguez de Castro Felipe , Ferreres José , Briones Marisa , Wauters Joost , Vanderbeke Lore , Feys Simon , Kuo Chen-Yen , Lei Wei-Te , Ku Cheng-Lung , Tal Galit , Etzioni Amos , Hanna Suhair , Fournet Thomas , Casalegno Jean-Sebastien , Queromes Gregory , Argaud Laurent , Javouhey Etienne , Rosa-Calatrava Manuel , Cordero Elisa , Aydillo Teresa , Medina Rafael A. , Kisand Kai , Puel Anne , Jouanguy Emmanuelle , Abel Laurent , Cobat Aurélie , Trouillet-Assant Sophie , García-Sastre Adolfo , Casanova Jean-Laurent 
Published: September 2022

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 &lt;70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10−5), but not &gt;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 &lt;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 &lt;70 yr old.