biostudies-literatureUnknownGervais ANCATS NIH HHSNIAID NIH HHSMosquito-borne West Nile virus (WNV) infection is a growing global health problem. About 0.5% of infected individuals develop encephalitis. We previously showed that 40% of patients in six cohorts had WNV encephalitis because of circulating auto-antibodies (auto-Abs) neutralizing type I IFNs. In seven new cohorts, we found that the prevalence of auto-Abs was highest (40% [17-44%]) in patients with encephalitis, and very low in a small sample of individuals with asymptomatic or mild infection. In the 13 European, Middle-Eastern and American cohorts available, odds ratios for WNV encephalitis in individuals with these auto-Abs relative to those without them in a large sample of the general population untested for WNV infection range from ~20 (OR=17.7; 95% CI: 13.8-22.8, <i>p</i><10<sup>-16</medRxiv : the preprint server for health sciences2025.08.31.25334556https://www.ebi.ac.uk/biostudies/studies/S-EPMC12424919biostudies-literatureAutoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts.PMC12424919R01 AI091707R01 AI124690R01 AI091816R01 AI163029UL1 TR001866U19 AI089992Lazzarotto TComoli PVogiatzis SPuel ABarzon LFreund TAngelini MGervais ABorghesi ADolci ACereda DRossini GLilleri DCassaniti IGhisetti VBastard PPacenti MAbel LCasanova JLMileto DCodullo VAubart MGadoth AMacDonald MRCroce SStiasny KAberle JHNagy ASimonin YBizien LBaldanti FParan YAiuti AFlorian DMZhang SYFerrari AConti FFellay JHagin DCobat APiralla AJouanguy EMoratti MMurray KOTrespidi FUhrlaub JLZecca MMarchal ARovida FBiran RAvanzini MALucca CMancon ARice CMBurdino EfalseAutoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts.Mosquito-borne West Nile virus (WNV) infection is a growing global health problem. About 0.5% of infected individuals develop encephalitis. We previously showed that 40% of patients in six cohorts had WNV encephalitis because of circulating auto-antibodies (auto-Abs) neutralizing type I IFNs. In seven new cohorts, we found that the prevalence of auto-Abs was highest (40% [17-44%]) in patients with encephalitis, and very low in a small sample of individuals with asymptomatic or mild infection. In the 13 European, Middle-Eastern and American cohorts available, odds ratios for WNV encephalitis in individuals with these auto-Abs relative to those without them in a large sample of the general population untested for WNV infection range from ~20 (OR=17.7; 95% CI: 13.8-22.8, <i>p</i><10<sup>-16</2025-01-01T00:00:00Z2025 Sep2026-05-26T20:06:38.3Z2026-05-26T03:06:26.634ZS-EPMC124249194095046810.1101/2025.08.31.25334556