Autoantibodies against type I IFNs in patients with critical influenza pneumonia

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, Tamara García-Salum, Marcela Ferres, Nicole Le CorreJavier Sánchez-Céspedes, María Balsera-Manzanero, Jordi Carratala, Pilar Retamar-Gentil, Gabriela Abelenda-Alonso, Adoración Valiente, Pierre Tiberghien, Marie Zins, Stéphanie Debette, Isabelle Meyts, Filomeen Haerynck, Riccardo Castagnoli, Luigi D. Notarangelo, Luis I. Gonzalez-Granado, Nerea Dominguez-Pinilla, Evangelos Andreakos, Vasiliki Triantafyllia, Carlos Rodríguez-Gallego, Jordi Solé-Violán, José Juan Ruiz-Hernandez, Felipe Rodríguez de Castro, 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 Casalegno, Gregory Queromes, Laurent Argaud, Etienne Javouhey, Manuel Rosa-Calatrava, Elisa Cordero, Teresa Aydillo, Rafael A. Medina, Kai Kisand, Anne Puel, Emmanuelle Jouanguy, Laurent Abel, Aurélie Cobat, Sophie Trouillet-Assant, Adolfo García-Sastre, Jean Laurent Casanova

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Article numbere20220514
JournalJournal of Experimental Medicine
Volume219
Issue number11
DOIs
StatePublished - 7 Nov 2022

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