Autoantibodies against type I IFNs in patients with critical influenza pneumonia
Author:
Zhang Qian123ORCID, Pizzorno Andrés4ORCID, Miorin Lisa56ORCID, Bastard Paul1237ORCID, Gervais Adrian23ORCID, Le Voyer Tom23ORCID, Bizien Lucy23ORCID, Manry Jeremy23ORCID, Rosain Jérémie23ORCID, Philippot Quentin23ORCID, Goavec Kelian23ORCID, Padey Blandine48ORCID, Cupic Anastasija5ORCID, Laurent Emilie49ORCID, Saker Kahina10ORCID, Vanker Martti11ORCID, Särekannu Karita11ORCID, 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, Morel Pascal, Richard Pascale, Bonneaudeau Brigitte, Cannet Dorothée, Gallian Pierre, Jeanne Michel, Perroquin Magali, Hamzeh-Cognasse Hind, Cognasse Fabrice, Tiberghien Pierre, Nadif Rachel, Goldberg Marcel, Ozguler Anna, Henny Joseph, Lemonnier Sylvie, Coeuret-Pellicer Mireille, Le Got Stéphane, Zins Marie, Tzourio Christophe, Debette Stéphanie, Dufouil Carole, Soumaré Aïcha, Lachaize Morgane, Fievet Nathalie, Flaig Amandine, Martin Fernando, Mehlal-Sedkaoui Souad, Sallette Jérôme, 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, 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 Tamara1213ORCID, Ferres Marcela12ORCID, Le Corre Nicole12ORCID, Sánchez-Céspedes Javier141516ORCID, Balsera-Manzanero María141516ORCID, Carratala Jordi141718ORCID, Retamar-Gentil Pilar141619ORCID, Abelenda-Alonso Gabriela1720ORCID, Valiente Adoración141519ORCID, Tiberghien Pierre21ORCID, Zins Marie22ORCID, Debette Stéphanie23ORCID, Meyts Isabelle24ORCID, Haerynck Filomeen25ORCID, Castagnoli Riccardo26ORCID, Notarangelo Luigi D.26ORCID, Gonzalez-Granado Luis I.27ORCID, Dominguez-Pinilla Nerea28ORCID, Andreakos Evangelos29ORCID, Triantafyllia Vasiliki29ORCID, Rodríguez-Gallego Carlos3031ORCID, Solé-Violán Jordi313233ORCID, Ruiz-Hernandez José Juan34ORCID, Rodríguez de Castro Felipe3536ORCID, Ferreres José3738ORCID, Briones Marisa39ORCID, Wauters Joost40ORCID, Vanderbeke Lore40ORCID, Feys Simon40ORCID, Kuo Chen-Yen4142ORCID, Lei Wei-Te4143ORCID, Ku Cheng-Lung414445ORCID, Tal Galit4647ORCID, Etzioni Amos46ORCID, Hanna Suhair46ORCID, Fournet Thomas48ORCID, Casalegno Jean-Sebastien49ORCID, Queromes Gregory4ORCID, Argaud Laurent50ORCID, Javouhey Etienne51ORCID, Rosa-Calatrava Manuel49ORCID, Cordero Elisa14151652ORCID, Aydillo Teresa56ORCID, Medina Rafael A.512ORCID, Kisand Kai11ORCID, Puel Anne123ORCID, Jouanguy Emmanuelle123ORCID, Abel Laurent123ORCID, Cobat Aurélie123ORCID, Trouillet-Assant Sophie410ORCID, García-Sastre Adolfo56535455ORCID, Casanova Jean-Laurent123756ORCID, , , , , , ,
Affiliation:
1. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 1 2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France 2 3. Université Paris Cité, Imagine Institute, Paris, France 3 4. CIRI, Centre International de Recherche en Infectiologie - Team VirPath, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France 4 5. Dept. of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 5 6. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 6 7. Dept. of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France 7 8. Signia Therapeutics SAS, Lyon, France 8 9. VirNext, Faculty of Medicine RTH Laennec, Claude Bernard Lyon 1 University, Lyon University, Lyon, France 9 10. Joint Research Unit, Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France 10 11. Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia 52 12. Dept. of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile 11 13. Pathology Advanced Translational Research Unit, Dept. of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 12 14. Center for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain 13 15. Infectious Diseases, Microbiology and Preventive Medicine, Virgen del Rocío University Hospital, Sevilla, Spain 14 16. Institute of Biomedicine of Seville (IBiS), CSIC, University of Seville, Seville, Spain 15 17. Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain 16 18. University of Barcelona, Barcelona, Spain 18 19. Infectious Diseases, Microbiology Unit, Virgen Macarena University Hospital, Seville, Spain 19 20. Dept. of Infectious Diseases, Bellvitge University Hospital, Barcelona, Spain 17 21. Etablissement Francais Du Sang, La Plaine-Saint Denis, Saint-Denis, France 20 22. University of Paris Cite, University of Paris-Saclay, UVSQ, INSERM UMS11, Villejuif, France 21 23. University of Bordeaux, INSERM, Bordeaux Population Health Center, UMR1219, Bordeaux, France 22 24. Laboratory for Inborn Errors of Immunity, Dept. of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium 23 25. Dept. of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent, PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium 24 26. Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 25 27. Immunodeficiencies Unit, Hospital October 12, Research Institute Hospital October 12, School of Medicine, Complutense University, Madrid, Spain 26 28. Pediatrics Service, Hematology and Oncology Unit, University Hospital 12 October, Madrid, Spain 27 29. Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece 28 30. Dept. of Immunology, University Hospital of Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain 29 31. Dept. of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain 30 32. Critical Care Unit, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain 31 33. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain 32 34. Dept. of Internal Medicine, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain 33 35. Dept. of Respiratory Diseases, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System, Las Palmas de Gran Canaria, Spain 34 36. Dept. of Medical and Surgical Sciences, School of Medicine, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain 35 37. Critical Care Unit, Hospital Clínico de Valencia, Valencia, Spain 36 38. INCLIVA Biomedical Research Institute, Valencia, Spain 37 39. Dept. of Respiratory Diseases, Hospital Clínico y Universitario de Valencia, Valencia, Spain 38 40. Dept. of General Internal Medicine, Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium 39 41. Laboratory of Human Immunology and Infectious Disease, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan 40 42. Division of Infectious Diseases, Dept. of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan 41 43. Dept. of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan 42 44. Dept. of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan 43 45. Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan 44 46. Metabolic Clinic, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel 45 47. Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel 46 48. Etablissement Français Du Sang, Université de Franche-Comté, Besançon, France 47 49. Virology Laboratory, CNR des Virus des Infections Respiratoires, Institut des Agents Infectieux, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France 48 50. Medical Intensive Care Dept., Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France 49 51. Pediatric Intensive Care Unit, Hospices Civils de Lyon, Hopital Femme Mère Enfant, Lyon, France 50 52. Dept. of Medicine, School of Medicine, University of Seville, Seville, Spain 51 53. Dept. of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 53 54. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 54 55. Dept. of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 55 56. Howard Hughes Medical Institute, New York, NY 56
Abstract
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.
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
31 articles.
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