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Six of 16 (37.5%) HSV-triggered FVH patients carried such auto-Abs on admission, including three with a previously known autoimmune disease. These patients contrasted with 133 HAV- (n = 46) or HBV-triggered (n = 87) patients, none of whom had such detectable auto-Abs. Odds ratios for HSV-triggered FVH in individuals with auto-Abs ranged from 35.3 (95% CI: 13.0\u201396.2; P &amp;lt; 10\u20137) for those neutralizing only 100 pg\/ml IFN-\u03b1\/\u03c9 to 1,895 (CI: 448.5\u20138,002; P &amp;lt; 10\u201312) for those neutralizing both IFN-\u03b1 and IFN-\u03c9 at 10 ng\/ml. Over one third of HSV-triggered FVH cases in this international cohort were due to preexisting auto-Abs. This finding highlights auto-Abs against type I IFNs as a major determinant of HSV-FVH and paves the way for targeted preventive or therapeutic interventions.<\/jats:p>","DOI":"10.1084\/jem.20251760","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T06:20:59Z","timestamp":1761632459000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Autoantibodies neutralizing type I IFNs in patients with fulminant herpes simplex virus hepatitis"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-5787","authenticated-orcid":true,"given":"Adrian","family":"Gervais","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02vjkv261","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1163, Necker 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