{"doi":"10.1084/jem.20220514","title":"Autoantibodies against type I IFNs in patients with critical influenza pneumonia","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.","journal":"The Journal of Experimental Medicine","year":2022,"id":233410,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":130,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":553952,"name":"Andrés Pizzorno","orcid":"0000-0002-0918-6804","position":1,"is_corresponding":false},{"id":2411,"name":"Lisa Miorin","orcid":"0000-0003-0989-3178","position":2,"is_corresponding":false},{"id":104138,"name":"Paul Bastard","orcid":"0000-0002-5926-8437","position":3,"is_corresponding":false},{"id":615375,"name":"Adrian Gervais","orcid":"0000-0002-1083-5787","position":4,"is_corresponding":false},{"id":618891,"name":"Tom Le Voyer","orcid":"0000-0002-7253-3135","position":5,"is_corresponding":false},{"id":104153,"name":"Lucy Bizien","orcid":"0000-0001-9163-9122","position":6,"is_corresponding":false},{"id":104148,"name":"Jérémy Manry","orcid":"0000-0001-5998-2051","position":7,"is_corresponding":false},{"id":104146,"name":"Jérémie Rosain","orcid":"0000-0002-2822-161X","position":8,"is_corresponding":false},{"id":104145,"name":"Quentin Philippot","orcid":"0000-0003-3429-9605","position":9,"is_corresponding":false},{"id":846451,"name":"Kelian Goavec","orcid":"0000-0002-0277-6692","position":10,"is_corresponding":false},{"id":630987,"name":"Blandine Padey","orcid":"0000-0002-2159-6507","position":11,"is_corresponding":false},{"id":2417,"name":"Anastasija Čupić","orcid":"0000-0002-1291-1042","position":12,"is_corresponding":false},{"id":846452,"name":"Emilie Laurent","orcid":"0000-0002-8993-8905","position":13,"is_corresponding":false},{"id":615386,"name":"Kahina Saker","orcid":"0000-0001-8825-5400","position":14,"is_corresponding":false},{"id":847347,"name":"Martti Vanker","orcid":null,"position":15,"is_corresponding":false},{"id":615379,"name":"Karita Särekannu","orcid":"0000-0002-5984-668X","position":16,"is_corresponding":false},{"id":104222,"name":"COVID Human Genetic Effort","orcid":null,"position":17,"is_corresponding":false},{"id":241301,"name":"Laurent Abel","orcid":"0000-0001-7016-6493","position":18,"is_corresponding":false},{"id":104170,"name":"Alessandro Aiuti","orcid":"0000-0002-5398-1717","position":19,"is_corresponding":false},{"id":243779,"name":"Saleh Al‐Muhsen","orcid":null,"position":20,"is_corresponding":false},{"id":104495,"name":"Fahd Al‐Mulla","orcid":"0000-0001-5409-3829","position":21,"is_corresponding":false},{"id":235418,"name":"Mark S. 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