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Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts

Title: Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts
Authors: Gervais, Adrian; Trespidi, Francesca; Ferrari, Alessandro; Rovida, Francesca; Marchal, Astrid; Croce, Stefania; Cassaniti, Irene; Moratti, Mattia; Uhrlaub, Jennifer L.; Florian, David M.; Stiasny, Karin; Burdino, Elisa; Angelini, Micol; Bizien, Lucy; Lilleri, Daniele; Codullo, Veronica; Freund, Tal; Paran, Yael; Gadoth, Avi; Biran, Roni; Mancon, Alessandro; Lucca, Camilla; Vogiatzis, Stefania; Pacenti, Monia; Aubart, Mélodie; Zecca, Marco; Comoli, Patrizia; Avanzini, Maria Antonietta; Fellay, Jacques; Piralla, Antonio; Conti, Francesca; Dolci, Alberto; Barzon, Luisa; Ghisetti, Valeria; Lazzarotto, Tiziana; Cereda, Danilo; Aiuti, Alessandro; Jouanguy, Emmanuelle; Bastard, Paul; MacDonald, Margaret R.; Rice, Charles M.; Puel, Anne; Abel, Laurent; Rossini, Giada; Mileto, Davide; Simonin, Yannick; Nagy, Anna; Hagin, David; Murray, Kristy O.; Baldanti, Fausto
Source: Journal of Human Immunity ; volume 2, issue 3 ; ISSN 3065-8993
Publisher Information: Rockefeller University Press
Publication Year: 2026
Description: 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 autoantibodies (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 (OR) 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, P < 10−16) for auto-Abs neutralizing only 100 pg/ml IFN-α2 and/or IFN-ω to >2,000 (OR = 2,218.4; 95% CI: 125.1–39,337.7, P < 10−16) for auto-Abs neutralizing high concentrations of IFN-α2 and high or low concentrations of IFN-ω. Preexisting auto-Abs neutralizing type I IFNs are therefore causal for WNV encephalitis in about 40% of patients.
Document Type: article in journal/newspaper
Language: English
DOI: 10.70962/jhi.20250189
DOI: 10.70962/jhi.20250189/2028254/jhi_20250189.pdf
Availability: https://doi.org/10.70962/jhi.20250189; https://rupress.org/jhi/article-pdf/doi/10.70962/jhi.20250189/2028254/jhi_20250189.pdf
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.C26795A1
Database: BASE