Autoantibodies against type I IFNs in patients with critical influenza pneumonia

• DOI: 10.1084/jem.20220514
• Publication Date: 2022-09-16T14:15:36Z
• Authors: Qian Zhang; Andrés Pizzorno; Lisa Miorin; Paul Bastard; Adrian Gervais; Tom Le Voyer; Lucy Bizien; Jeremy Manry; Jérémie Rosain; Quentin Philippot; Kelian Goavec; Blandine Padey; Anastasija Cupic; 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 Bondar...; Ahmed A. Bousfiha; Petter Brodin; Yenan Bryceson; Carlos D. Bustamante; Manish J. Butte; Giorgio Casari; John Christodoulou; Antonio Condino-Neto; Stefan N. Constan...; Megan A. Cooper; Clifton L. Dalgard; Murkesh Desai; Beth A. Drolet; Jamila El Baghdadi; Sara Espinosa-Pad...; Jacques Fellay; Carlos Flores; Paraskevi C. Fragkou; José Luis Franco; Antoine Froidure; Ioanna Evdokia Ga...; 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 Karami...; Kai Kisand; Ourania Koltsida; Cheng-Lung Ku; Yu-Lung Lau; Yun Ling; Carrie L. 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 O'Farrelly; Satoshi Okada; Keisuke Okamoto; Tayfun Ozcelik; Qiang Pan-Hammars...; Jean W. Pape; Rebeca Perez de D...; David S. Perlin; Graziano Pesole; Anna M. Planas; Carolina Prando; Aurora Pujol; Lluis Quintana-Murci; Sathishkumar Rama...; Vasiliki Rapti; Laurent Renia; Igor Resnick; Carlos Rodríguez-...; Nikoletta Rovina; Vanessa Sancho-Sh...; Anna Sediva; Mikko R.J. Seppänen; Mohammed Shahrooei; Anna Shcherbina; Ondrej Slaby; 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 J. Uddin; Diederik van de Beek; Donald C. Vinh; Horst von Bernuth; Joost Wauters; Mayana Zatz; Pawel Zawadzki; Helen C. Su; Jean-Laurent Casa...; ; 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 Coeuret-...; Stéphane Le Got; Marie Zins; ; Christophe Tzourio; Stéphanie Debette; Carole Dufouil; Aïcha Soumaré; Morgane Lachaize; Nathalie Fievet; Amandine Flaig; ; Fernando Martin; Souad Mehlal-Sedk...; Jérôme Sallette; ; Romain Hernu; Bruno Lina; Carole Schwebel; Isabelle Wroblewski; Patrice Morand; Bertrand Souweine; Benoit Boeuf; Helene Peigue-Laf...; Michael Darmon; Hugues Patural; Bruno Pozzetto; Jean Pierre Quenot; Benoit Colomb; Pierre Pothier; Alexandre Belot; ; Maria Abad Arranz; Manuela Aguilar G...; Ana Escoresca Ortega; Rafaela Gallardo ...; Laura Merino Díaz; Maria Del Mar Muñ...; Nieves Ramírez Duque; Gloria María Rome...; Maria Jose Sánche...; Celia Salamanca R...; Jordi Niubó; Alexander Rombauts; Nicolás Navarrete; Laura Romero Oraa; Virginia Palomo; Tamara García-Salum; Marcela Ferres; Nicole Le Corre; Javier Sánchez-Cé...; María Balsera-Man...; Jordi Carratala; Pilar Retamar-Gentil; Gabriela Abelenda...; Adoración Valiente; Pierre Tiberghien; Marie Zins; Stéphanie Debette; Isabelle Meyts; Filomeen Haerynck; Riccardo Castagnoli; Luigi D. Notarangelo; Luis I. Gonzalez-...; Nerea Dominguez-P...; Evangelos Andreakos; Vasiliki Triantaf...; Carlos Rodríguez-...; Jordi Solé-Violán; José Juan Ruiz-He...; Felipe Rodríguez ...; José Ferreres; Marisa Briones; Joost Wauters; Lore Vanderbeke; Simon Feys; Chen-Yen Kuo; Wei-Te Lei; Cheng-Lung Ku; Galit Tal; Amos Etzioni; Suhair Hanna; Thomas Fournet; Jean-Sebastien Ca...; Gregory Queromes; Laurent Argaud; Etienne Javouhey; Manuel Rosa-Calat...; Elisa Cordero; Teresa Aydillo; Rafael A. Medina; Kai Kisand; Anne Puel; Emmanuelle Jouanguy; Laurent Abel; Aurélie Cobat; Sophie Trouillet-...; Adolfo García-Sastre; Jean-Laurent Casa...
• Keywords: 0301 basic medicine; Informe de Investigación; Virus de la Influenza A; SEVERE COVID-19; Pneumònia; DETERMINANTS; Autoanticossos; Settore MED/03 - GENETICA MEDICA; Virus Replication; 3C-Dijon Study; 03 Salud y bienestar; INFECTION; Medicine and Health Sciences; Prevalence; MYASTHENIA-GRAVIS PATIENTS; REIPI INF Working Group; Yellow Fever Vaccine; Autoanticuerpos; Influenza A virus; Influenza Vaccines; Interferon Type I; [SDV.IMM]Life Sciences [q-bio]/Immunology; BURDEN; Constances Cohort; INTERFERON; Cerba HealthCare Group; Anticuerpos; SARS-Cov-2; 610; IMMUNITY; Antibodies; Article; NEUTRALIZING ANTIBODIES; Grip; Vacuna contra la Fiebre Amarilla; 03 medical and health sciences; 616; Neumonía; Influenza, Human; [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]; Gripe Humana; Type I interferons; Interferón Tipo I; Humans; COVID Human Genetic Effort; 320505 Enfermedades infecciosas; Autoantibodies; Células A549; [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics; Etablissement Français du Sang Study Group; COVID-19; Pneumonia; ALLELES; Lyon Antigrippe Working Group; Influenza; ALPHA; A549 Cells; 03 Good Health and Well-being; 32 Ciencias médicas

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.