Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients

Gervais 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.