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Autoantibodies against type I IFNs in patients with critical influenza pneumonia

Zhang, Q (author)
Pizzorno, A (author)
Miorin, L (author)
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Bastard, P (author)
Gervais, A (author)
Le Voyer, T (author)
Bizien, L (author)
Manry, J (author)
Rosain, J (author)
Philippot, Q (author)
Goavec, K (author)
Padey, B (author)
Cupic, A (author)
Laurent, E (author)
Saker, K (author)
Vanker, M (author)
Sarekannu, K (author)
Garcia-Salum, T (author)
Ferres, M (author)
Le Corre, N (author)
Sanchez-Cespedes, J (author)
Balsera-Manzanero, M (author)
Carratala, J (author)
Retamar-Gentil, P (author)
Abelenda-Alonso, G (author)
Valiente, A (author)
Tiberghien, P (author)
Zins, M (author)
Debette, S (author)
Meyts, I (author)
Haerynck, F (author)
Castagnoli, R (author)
Notarangelo, LD (author)
Gonzalez-Granado, LI (author)
Dominguez-Pinilla, N (author)
Andreakos, E (author)
Triantafyllia, V (author)
Rodriguez-Gallego, C (author)
Sole-Violan, J (author)
Ruiz-Hernandez, JJ (author)
Rodriguez de Castro, F (author)
Ferreres, J (author)
Briones, M (author)
Wauters, J (author)
Vanderbeke, L (author)
Feys, S (author)
Kuo, CY (author)
Lei, WT (author)
Ku, CL (author)
Tal, G (author)
Etzioni, A (author)
Hanna, S (author)
Fournet, T (author)
Casalegno, JS (author)
Queromes, G (author)
Argaud, L (author)
Javouhey, E (author)
Rosa-Calatrava, M (author)
Cordero, E (author)
Aydillo, T (author)
Medina, RA (author)
Kisand, K (author)
Puel, A (author)
Jouanguy, E (author)
Abel, L (author)
Cobat, A (author)
Trouillet-Assant, S (author)
Garcia-Sastre, A (author)
Casanova, JL (author)
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2022-09-16
2022
English.
In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:11
Related links:
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

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