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Causality between these AAN-I-IFN and lethal outcome of avian influenza in this patient is based on (1) our previous report that AA-I-IFN underlie about 5% of cases of critical pneumonia triggered by seasonal influenza viruses in three cohorts, (2) the rarity of this combination of AAN-I-FNs in individuals over 70 years old (&amp;lt;1%), and (3) the rarity of lethal avian influenza among infected individuals (&amp;lt;1%). AAN-I-IFNs underlie a growing number of severe viral diseases, from arboviral encephalitis to viral pneumonia, particularly in the elderly. This case suggests they can also underlie life-threatening avian H5N1 influenza. The presence of AAN-I-IFN may facilitate infection, replication, and adaptation of zoonotic IAVs to humans and, therefore, human-to-human transmission.<\/jats:p>","DOI":"10.1084\/jem.20251962","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T07:20:53Z","timestamp":1763450453000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Autoantibodies neutralizing type I IFNs in a fatal case of H5N1 avian influenza"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9040-3289","authenticated-orcid":true,"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0420db125","id-type":"ROR","asserted-by":"publisher"}],"name":"The Rockefeller University 1 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, , New York, 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