Autoantibodies against type I IFNs in patients with critical influenza pneumonia

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.

In:The Journal of experimental medicine: Rockefeller University Press219:111540-95380022-1007

By the author/editor: Zhang, Q; Pizzorno, A; Miorin, L; Bastard, P; Gervais, A; Le Voyer, T; show more...; Bizien, L; Manry, J; Rosain, J; Philippot, Q; Goavec, K; Padey, B; Cupic, A; Laurent, E; Saker, K; Vanker, M; Sarekannu, K; Garcia-Salum, T; Ferres, M; Le Corre, N; Sanchez-Cespedes ...; Balsera-Manzaner ...; Carratala, J; Retamar-Gentil, ...; Abelenda-Alonso, ...; Valiente, A; Tiberghien, P; Zins, M; Debette, S; Meyts, I; Haerynck, F; Castagnoli, R; Notarangelo, LD; Gonzalez-Granado ...; Dominguez-Pinill ...; Andreakos, E; Triantafyllia, V; Rodriguez-Galleg ...; Sole-Violan, J; Ruiz-Hernandez, ...; Rodriguez de Cas ...; Ferreres, J; Briones, M; Wauters, J; Vanderbeke, L; Feys, S; Kuo, CY; Lei, WT; Ku, CL; Tal, G; Etzioni, A; Hanna, S; Fournet, T; Casalegno, JS; Queromes, G; Argaud, L; Javouhey, E; Rosa-Calatrava, ...; Cordero, E; Aydillo, T; Medina, RA; Kisand, K; Puel, A; Jouanguy, E; Abel, L; Cobat, A; Trouillet-Assant ...; Garcia-Sastre, A; Casanova, JL; show less...

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