Zhang, QianGonzález Granado, Luis IgnacioCasanova, Jean Laurent2026-07-072026-07-072022-11-07Zhang 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: PMC9485705.0022-100710.1084/jem.20220514https://hdl.handle.net/20.500.14352/138092This 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1540-9538https://doi.org/10.1084/jem.2022051436112363https://rupress.org/jem/article/219/11/e20220514/213469/Autoantibodies-against-type-I-IFNs-in-patientshttps://pubmed.ncbi.nlm.nih.gov/36112363/open access612.017616‑053.2Type I interferonIFN-alphaIFN-omegaAutoantibodiesNeutralizing autoantibodiesInfluenzaCritical influenza pneumoniaViral pneumoniaInborn errors of immunityImmune dysregulationAntiviral immunityMedicinaInmunologíaPediatríaEnfermedades infecciosasBiología molecular (Biología)2412 Inmunología3201 Ciencias Clínicas3201.10 Pediatría3201.03 Microbiología Clínica2415 Biología Molecular