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

Adrian Gervais; Francesca Rovida; Maria Antonietta Avanzini; Stefania Croce; Astrid Marchal; Shih-Ching Lin; Alessandro Ferrari; Christian W Thorball; Orianne Constant; Tom Le Voyer; Quentin Philippot; Jérémie Rosain; Micol Angelini; Malena Pérez Lorenzo; Lucy Bizien; Cristian Achille; Francesca Trespidi; Elisa Burdino; Irene Cassaniti; Daniele Lilleri; Chiara Fornara; José Camilla Sammartino; Danilo Cereda; Chiara Marrocu; Antonio Piralla; Chiara Valsecchi; Stefano Ricagno; Paola Cogo; Olaf Neth; Inés Marín-Cruz; Monia Pacenti; Alessandro Sinigaglia; Marta Trevisan; Andrea Volpe; Antonio Marzollo; Francesca Conti; Tiziana Lazzarotto; Andrea Pession; Pierluigi Viale; Jacques Fellay; Stefano Ghirardello; Mélodie Aubart; Valeria Ghisetti; Alessandro Aiuti; Emmanuelle Jouanguy; Paul Bastard; Elena Percivalle; Fausto Baldanti; Anne Puel; Margaret R Macdonald; Charles M Rice; Giada Rossini; Kristy O Murray; Yannick Simonin; Anna Nagy; Luisa Barzon; Laurent Abel; Michael S Diamond; Aurélie Cobat; Shen-Ying Zhang; Jean-Laurent Casanova; Alessandro Borghesi

doi:10.1084/jem.20230661

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

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

Adrian Gervais, Francesca Rovida, Maria Antonietta Avanzini, Stefania Croce, Astrid Marchal, Shih-Ching Lin, Alessandro Ferrari, Christian W Thorball, Orianne Constant, Tom Le Voyer, …

Journal of Experimental Medicine, Vol.220(9)

22/06/2023

DOI: https://doi.org/10.1084/jem.20230661

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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Title: Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients
Creators - without role: Adrian Gervais - Université Paris Cité
Francesca Rovida - Policlinico San Matteo Fondazione
Maria Antonietta Avanzini - University of Pavia
Stefania Croce
Astrid Marchal - Inserm
Shih-Ching Lin
Alessandro Ferrari - Policlinico San Matteo Fondazione
Christian W Thorball - University of Lausanne
Orianne Constant - Université de Montpellier
Tom Le Voyer - Inserm
Quentin Philippot - Inserm
Jérémie Rosain - Inserm
Micol Angelini - Policlinico San Matteo Fondazione
Malena Pérez Lorenzo - Imagine - Institut des maladies génétiques (IHU)
Lucy Bizien - Inserm
Cristian Achille - Policlinico San Matteo Fondazione
Francesca Trespidi - Policlinico San Matteo Fondazione
Elisa Burdino - Ospedale Amedeo di Savoia
Irene Cassaniti - Policlinico San Matteo Fondazione
Daniele Lilleri - Policlinico San Matteo Fondazione
Chiara Fornara - Policlinico San Matteo Fondazione
José Camilla Sammartino - Policlinico San Matteo Fondazione
Danilo Cereda - Ministero della Salute
Chiara Marrocu - University of Milan
Antonio Piralla - Policlinico San Matteo Fondazione
Chiara Valsecchi - University of Pavia
Stefano Ricagno - University of Milan
Paola Cogo - University of Udine
Olaf Neth - Instituto de Biomedicina de Sevilla
Inés Marín-Cruz - Hospital Universitario Virgen del Rocío
Monia Pacenti - University of Padua
Alessandro Sinigaglia - University of Padua
Marta Trevisan - University of Padua
Andrea Volpe - University of Padua
Antonio Marzollo - University of Padua
Francesca Conti - University of Bologna
Tiziana Lazzarotto - Azienda USL di Bologna
Andrea Pession - University of Bologna
Pierluigi Viale - University of Bologna
Jacques Fellay - University of Lausanne
Stefano Ghirardello - Policlinico San Matteo Fondazione
Mélodie Aubart - Inserm
Valeria Ghisetti - Ospedale Amedeo di Savoia
Alessandro Aiuti - Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
Emmanuelle Jouanguy - Inserm
Paul Bastard - Inserm
Elena Percivalle - Policlinico San Matteo Fondazione
Fausto Baldanti - University of Pavia
Anne Puel - Inserm
Margaret R Macdonald - Rockefeller University
Charles M Rice - Rockefeller University
Giada Rossini - Azienda USL di Bologna
Kristy O Murray - Texas Children's Hospital
Yannick Simonin - Université de Montpellier, Pathogenesis and Control of Chronic and Emerging Infections - PCCEI
Anna Nagy - National Center for Epidemiology
Luisa Barzon - University of Padua
Laurent Abel - Inserm
Michael S Diamond
Aurélie Cobat - Inserm
Shen-Ying Zhang - Imagine - Institut des maladies génétiques (IHU)
Jean-Laurent Casanova - Imagine - Institut des maladies génétiques (IHU)
Alessandro Borghesi - École Polytechnique Fédérale de Lausanne
Publication Details: Journal of Experimental Medicine, Vol.220(9)
Identifiers: 9939041609311
Academic Unit: Pathogenesis and Control of Chronic and Emerging Infections - PCCEI
Language: English
Resource Type: Journal article
Local Fields: hal-04229658