Gervais, AdrianRovida, FrancescaAvanzini, Maria AntoniettaCroce, StefaniaMarchal, AstridLin, Shih-ChingFerrari, AlessandroThorball, Christian W.Constant, OrianneLe Voyer, TomPhilippot, QuentinRosain, JeremieAngelini, MicolLorenzo, Malena PerezBizien, LucyAchille, CristianTrespidi, FrancescaBurdino, ElisaCassaniti, IreneLilleri, DanieleFornara, ChiaraSammartino, Jose CamillaCereda, DaniloMarrocu, ChiaraPiralla, AntonioValsecchi, ChiaraRicagno, StefanoCogo, PaolaNeth, OlafMarin-Cruz, InesPacenti, MoniaSinigaglia, AlessandroTrevisan, MartaVolpe, AndreaMarzollo, AntonioConti, FrancescaLazzarotto, TizianaPession, AndreaViale, PierluigiFellay, JacquesGhirardello, StefanoAubart, MelodieGhisetti, ValeriaAiuti, AlessandroJouanguy, EmmanuelleBastard, PaulPercivalle, ElenaBaldanti, FaustoPuel, AnneMacDonald, Margaret R.Rice, Charles M.Rossini, GiadaMurray, Kristy O.Simonin, YannickNagy, AnnaBarzon, LuisaAbel, LaurentDiamond, Michael S.Cobat, AurelieZhang, Shen-YingCasanova, Jean-LaurentBorghesi, Alessandro2023-08-282023-08-282023-08-282023-06-2210.1084/jem.20230661https://infoscience.epfl.ch/handle/20.500.14299/200313WOS:001017263000001Gervais et al. show that auto-Abs neutralizing type I IFNs and pre-existing infection underlie & SIM;40% of cases of West Nile virus (WNV) encephalitis. Blood and cerebrospinal fluid auto-Abs neutralize the protective activity of type I IFNs against WNV in vitro.Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that & SIM;35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-& alpha; and/or -& omega;. The prevalence of these antibodies is highest in patients with encephalitis (& SIM;40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10(-15)) for auto-Abs neutralizing only 100 pg/ml IFN-& alpha; and/or IFN-& omega; to 127.4 (CI 87.1-186.4, P value <10(-15)) for auto-Abs neutralizing both IFN-& alpha; and IFN-& omega; at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-& alpha; in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-& alpha; and/or IFN-& omega; underlie & SIM;40% of cases of WNV encephalitis.ImmunologyMedicine, Research & ExperimentalResearch & Experimental Medicinerisk-factorsunited-statesnew-yorkinfectiondiseaseinterferonsurveillanceantibodiesepidemicchildtext::journal::journal article::research article