Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼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-α and/or IFN-ω to 127.4 (CI 87.1–186.4, P value <10–15 ) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.
Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients / A. Gervais, F. Rovida, M.A. Avanzini, S. Croce, A. Marchal, S. Lin, A. Ferrari, C. Thorball, O. Constant, T. Le Voyer, Q. Philippot, J. Rosain, M. Angelini, M. Pérez Lorenzo, L. Bizien, C. Achille, F. Trespidi, E. Burdino, I. Cassaniti, D. Lilleri, C. Fornara, J.C. Sammartino, D. Cereda, C. Marrocu, A. Piralla, C. Valsecchi, S. Ricagno, P. Cogo, O. Neth, I. Marín-Cruz, M. Pacenti, A. Sinigaglia, M. Trevisan, A. Volpe, A. Marzollo, F. Conti, T. Lazzarotto, A. Pession, P. Viale, J. Fellay, S. Ghirardello, M. Aubart, V. Ghisetti, A. Aiuti, E. Jouanguy, P. Bastard, E. Percivalle, F. Baldanti, A. Puel, M. Macdonald, C. Rice, G. Rossini, K. Murray, Y. Simonin, A. Nagy, L. Barzon, L. Abel, M. Diamond, A. Cobat, S. Zhang, J. Casanova, A. Borghesi. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - 220:9(2023 Sep), pp. e20230661.1-e20230661.24. [10.1084/jem.20230661]
Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients
C. Marrocu;S. Ricagno;
2023
Abstract
Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼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-α and/or IFN-ω to 127.4 (CI 87.1–186.4, P value <10–15 ) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.
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