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oai:docta.ucm.es:20.500.14352/1380922026-07-08T00:15:13Zcom_20.500.14352_14col_20.500.14352_15

Autoantibodies against type I IFNs in patients with critical influenza pneumonia. Zhang, Qian González Granado, Luis Ignacio Casanova, Jean Laurent 612.017 616‑053.2 Type I interferon IFN-alpha IFN-omega Autoantibodies Neutralizing autoantibodies Influenza Critical influenza pneumonia Viral pneumonia Inborn errors of immunity Immune dysregulation Antiviral immunity Medicina Inmunología Pediatría Enfermedades infecciosas Biología molecular (Biología) 2412 Inmunología 3201 Ciencias Clínicas 3201.10 Pediatría 3201.03 Microbiología Clínica 2415 Biología Molecular This study investigates neutralizing autoantibodies against type I interferons in patients with critical influenza pneumonia. In a cohort of 279 patients aged 6 to 73 years with critical influenza pneumonia, autoantibodies neutralizing IFN-α2 alone or both IFN-α2 and IFN-ω were identified in a subset of patients. The work shows that these autoantibodies are enriched among patients with life-threatening influenza, particularly in individuals under 70 years of age, and supports a causal role of impaired type I interferon immunity in 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. Depto. de Salud Pública y Materno - Infantil Fac. de Medicina TRUE pub 2026-07-07T08:01:05Z 2026-07-07T08:01:05Z 2022-11-07 journal article VoR https://hdl.handle.net/20.500.14352/138092 0022-1007 10.1084/jem.20220514 1540-9538 eng Zhang Q, Pizzorno A, Miorin L, Bastard P, Gervais A, Le Voyer T, et al. Autoantibodies against type I IFNs in patients with critical influenza pneumonia. J Exp Med. 2022 Nov 7;219(11):e20220514. doi: 10.1084/jem.20220514. PMID: 36112363; PMCID: PMC9485705. Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ open access application/pdf Rockefeller University Press