학술논문
Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients
Document Type
Article
Author
Gervais, Adrian; Rovida, Francesca; Avanzini, Maria Antonietta; Croce, Stefania; Marchal, Astrid; Lin, Shih-Ching; Ferrari, Alessandro; Thorball, Christian W.; Constant, Orianne; Le Voyer, Tom; Philippot, Quentin; Rosain, Jérémie; Angelini, Micol; Pérez Lorenzo, Malena; Bizien, Lucy; Achille, Cristian; Trespidi, Francesca; Burdino, Elisa; Cassaniti, Irene; Lilleri, Daniele; Fornara, Chiara; Sammartino, José Camilla; Cereda, Danilo; Marrocu, Chiara; Piralla, Antonio; Valsecchi, Chiara; Ricagno, Stefano; Cogo, Paola; Neth, Olaf; Marín-Cruz, Inés; Pacenti, Monia; Sinigaglia, Alessandro; Trevisan, Marta; Volpe, Andrea; Marzollo, Antonio; Conti, Francesca; Lazzarotto, Tiziana; Pession, Andrea; Viale, Pierluigi; Fellay, Jacques; Ghirardello, Stefano; Aubart, Mélodie; Ghisetti, Valeria; Aiuti, Alessandro; Jouanguy, Emmanuelle; Bastard, Paul; Percivalle, Elena; Baldanti, Fausto; Puel, Anne; MacDonald, Margaret R.; Rice, Charles M.; Rossini, Giada; Murray, Kristy O.; Simonin, Yannick; Nagy, Anna; Barzon, Luisa; Abel, Laurent; Diamond, Michael S.; Cobat, Aurélie; Zhang, Shen-Ying; Casanova, Jean-Laurent; Borghesi, Alessandro
Source
The Journal of Experimental Medicine; September 2023, Vol. 220 Issue: 9 pe20230661-e20230661, 1p
Subject
Language
ISSN
00221007; 15409538
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.