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Thus, IFN\u2010I deficiencies are associated with serious life\u2010threatening infections. Remarkably, some rare individuals with chronic autoimmune diseases develop neutralizing autoantibodies (autoAbs) against IFN\u2010Is thereby compromising their own innate antiviral defenses. Furthermore, the prevalence of anti\u2010IFN\u2010I autoAbs in apparently healthy individuals increases with age, such that \u223c4% of those over 70 years old are affected. Here, I review the literature on factors that may predispose individuals to develop anti\u2010IFN\u2010I autoAbs, such as reduced self\u2010tolerance caused by defects in the genes\n                    <jats:italic>AIRE<\/jats:italic>\n                    ,\n                    <jats:italic>NFKB2<\/jats:italic>\n                    , and\n                    <jats:italic>FOXP3<\/jats:italic>\n                    (among others), or by generally impaired thymus function, including thymic involution in the elderly. In addition, I discuss the hypothesis that predisposed individuals develop anti\u2010IFN\u2010I autoAbs following \u201cautoimmunization\u201d with IFN\u2010Is generated during some acute viral infections, systemic inflammatory events, or chronic IFN\u2010I exposure. Finally, I highlight the enhanced susceptibility that individuals with anti\u2010IFN\u2010I autoAbs appear to have towards viral diseases such as severe COVID\u201019, influenza, or herpes (e.g., varicella\u2010zoster virus, herpes simplex virus, cytomegalovirus), as well as adverse reactions to live\u2010attenuated vaccines. Understanding the mechanisms underlying development and consequences of anti\u2010IFN\u2010I autoAbs will be key to implementing effective prophylactic and therapeutic measures.\n                  <\/jats:p>","DOI":"10.1002\/eji.202250164","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T13:04:15Z","timestamp":1680872655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Autoantibodies targeting type I interferons: Prevalence, mechanisms of induction, and association with viral disease susceptibility"],"prefix":"10.1002","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3891-9480","authenticated-orcid":false,"given":"Benjamin G.","family":"Hale","sequence":"first","affiliation":[{"name":"Institute of Medical Virology University of Zurich  Winterthurerstrasse 190, 8057 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0421-x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2021.03.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048793"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.08.017"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl4340"},{"key":"e_1_2_10_7_1","first-page":"370","article-title":"Autoantibodies against type I IFNs in patients with life\u2010threatening COVID\u201019","author":"Bastard 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