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

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 LilleriChiara 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

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

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.

Original language	English
Journal	The Journal of experimental medicine
Volume	220
Issue number	9
DOIs	https://doi.org/10.1084/jem.20230661
State	Published - Sep 4 2023

Access to Document

10.1084/jem.20230661

Cite this

Gervais, A., Rovida, F., Avanzini, M. A., Croce, S., Marchal, A., Lin, S. C., Ferrari, A., Thorball, C. W., Constant, O., Le Voyer, T., Philippot, Q., Rosain, J., Angelini, M., Pérez Lorenzo, M., Bizien, L., Achille, C., Trespidi, F., Burdino, E., Cassaniti, I., ... Borghesi, A. (2023). Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients. The Journal of experimental medicine, 220(9). https://doi.org/10.1084/jem.20230661

@article{44bfd3fee14546f89d61aaf43cf81ff0,

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

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.",

author = "Adrian Gervais and Francesca Rovida and Avanzini, {Maria Antonietta} and Stefania Croce and Astrid Marchal and Lin, {Shih Ching} and Alessandro Ferrari and Thorball, {Christian W.} and Orianne Constant and {Le Voyer}, Tom and Quentin Philippot and J{\'e}r{\'e}mie Rosain and Micol Angelini and {P{\'e}rez Lorenzo}, Malena and Lucy Bizien and Cristian Achille and Francesca Trespidi and Elisa Burdino and Irene Cassaniti and Daniele Lilleri and Chiara Fornara and Sammartino, {Jos{\'e} Camilla} and Danilo Cereda and Chiara Marrocu and Antonio Piralla and Chiara Valsecchi and Stefano Ricagno and Paola Cogo and Olaf Neth and In{\'e}s Mar{\'i}n-Cruz and Monia Pacenti and Alessandro Sinigaglia and Marta Trevisan and Andrea Volpe and Antonio Marzollo and Francesca Conti and Tiziana Lazzarotto and Andrea Pession and Pierluigi Viale and Jacques Fellay and Stefano Ghirardello and M{\'e}lodie Aubart and Valeria Ghisetti and Alessandro Aiuti and Emmanuelle Jouanguy and Paul Bastard and Elena Percivalle and Fausto Baldanti and Anne Puel and MacDonald, {Margaret R.} and Rice, {Charles M.} and Giada Rossini and Murray, {Kristy O.} and Yannick Simonin and Anna Nagy and Luisa Barzon and Laurent Abel and Diamond, {Michael S.} and Aur{\'e}lie Cobat and Zhang, {Shen Ying} and Casanova, {Jean Laurent} and Alessandro Borghesi",

note = "Publisher Copyright: {\textcopyright} 2023 Gervais et al.",

year = "2023",

month = sep,

day = "4",

doi = "10.1084/jem.20230661",

language = "English",

volume = "220",

journal = "The Journal of experimental medicine",

issn = "0022-1007",

number = "9",

}

Gervais, A, Rovida, F, Avanzini, MA, Croce, S, Marchal, A, Lin, SC, Ferrari, A, Thorball, CW, Constant, O, Le Voyer, T, Philippot, Q, Rosain, J, Angelini, M, Pérez Lorenzo, M, Bizien, L, Achille, C, Trespidi, F, Burdino, E, Cassaniti, I, Lilleri, D, Fornara, C, Sammartino, JC, Cereda, D, Marrocu, C, Piralla, A, Valsecchi, C, Ricagno, S, Cogo, P, Neth, O, Marín-Cruz, I, Pacenti, M, Sinigaglia, A, Trevisan, M, Volpe, A, Marzollo, A, Conti, F, Lazzarotto, T, Pession, A, Viale, P, Fellay, J, Ghirardello, S, Aubart, M, Ghisetti, V, Aiuti, A, Jouanguy, E, Bastard, P, Percivalle, E, Baldanti, F, Puel, A, MacDonald, MR, Rice, CM, Rossini, G, Murray, KO, Simonin, Y, Nagy, A, Barzon, L, Abel, L, Diamond, MS, Cobat, A, Zhang, SY, Casanova, JL & Borghesi, A 2023, 'Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients', The Journal of experimental medicine, vol. 220, no. 9. https://doi.org/10.1084/jem.20230661

TY - JOUR

T1 - Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients

AU - Gervais, Adrian

AU - Rovida, Francesca

AU - Avanzini, Maria Antonietta

AU - Croce, Stefania

AU - Marchal, Astrid

AU - Lin, Shih Ching

AU - Ferrari, Alessandro

AU - Thorball, Christian W.

AU - Constant, Orianne

AU - Le Voyer, Tom

AU - Philippot, Quentin

AU - Rosain, Jérémie

AU - Angelini, Micol

AU - Pérez Lorenzo, Malena

AU - Bizien, Lucy

AU - Achille, Cristian

AU - Trespidi, Francesca

AU - Burdino, Elisa

AU - Cassaniti, Irene

AU - Lilleri, Daniele

AU - Fornara, Chiara

AU - Sammartino, José Camilla

AU - Cereda, Danilo

AU - Marrocu, Chiara

AU - Piralla, Antonio

AU - Valsecchi, Chiara

AU - Ricagno, Stefano

AU - Cogo, Paola

AU - Neth, Olaf

AU - Marín-Cruz, Inés

AU - Pacenti, Monia

AU - Sinigaglia, Alessandro

AU - Trevisan, Marta

AU - Volpe, Andrea

AU - Marzollo, Antonio

AU - Conti, Francesca

AU - Lazzarotto, Tiziana

AU - Pession, Andrea

AU - Viale, Pierluigi

AU - Fellay, Jacques

AU - Ghirardello, Stefano

AU - Aubart, Mélodie

AU - Ghisetti, Valeria

AU - Aiuti, Alessandro

AU - Jouanguy, Emmanuelle

AU - Bastard, Paul

AU - Percivalle, Elena

AU - Baldanti, Fausto

AU - Puel, Anne

AU - MacDonald, Margaret R.

AU - Rice, Charles M.

AU - Rossini, Giada

AU - Murray, Kristy O.

AU - Simonin, Yannick

AU - Nagy, Anna

AU - Barzon, Luisa

AU - Abel, Laurent

AU - Diamond, Michael S.

AU - Cobat, Aurélie

AU - Zhang, Shen Ying

AU - Casanova, Jean Laurent

AU - Borghesi, Alessandro

PY - 2023/9/4

Y1 - 2023/9/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85164041846&partnerID=8YFLogxK

U2 - 10.1084/jem.20230661

DO - 10.1084/jem.20230661

M3 - Article

C2 - 37347462

AN - SCOPUS:85164041846

SN - 0022-1007

VL - 220

JO - The Journal of experimental medicine

JF - The Journal of experimental medicine

IS - 9

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this