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Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine\u2013associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-\u03b12 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.<\/jats:p>","DOI":"10.1084\/jem.20202486","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T02:21:37Z","timestamp":1611109297000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":256,"title":["Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5926-8437","authenticated-orcid":true,"given":"Paul","family":"Bastard","sequence":"first","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1163, Necker Hospital for Sick Children, Paris, France 1"},{"name":"University of Paris, Imagine Institute, Paris, France 2"},{"name":"St. Giles Laboratory of Human 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