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 / 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.; Perez Lorenzo M.; Bizien L.; Achille C.; Trespidi F.; Burdino E.; Cassaniti I.; Lilleri D.; Fornara C.; Sammartino J.C.; Cereda D.; Marrocu C.; Piralla A.; Valsecchi C.; Ricagno S.; Cogo P.; Neth O.; Marin-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 M.R.; Rice C.M.; Rossini G.; Murray K.O.; Simonin Y.; Nagy A.; Barzon L.; Abel L.; Diamond M.S.; Cobat A.; Zhang S.-Y.; Casanova J.-L.; Borghesi A.. - In: THE JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 1540-9538. - ELETTRONICO. - 220:9(2023), pp. e20230661.1-e20230661.24. [10.1084/jem.20230661]

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

Valsecchi C.;Conti F.;Lazzarotto T.;Viale P.;
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.
2023
Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients / 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.; Perez Lorenzo M.; Bizien L.; Achille C.; Trespidi F.; Burdino E.; Cassaniti I.; Lilleri D.; Fornara C.; Sammartino J.C.; Cereda D.; Marrocu C.; Piralla A.; Valsecchi C.; Ricagno S.; Cogo P.; Neth O.; Marin-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 M.R.; Rice C.M.; Rossini G.; Murray K.O.; Simonin Y.; Nagy A.; Barzon L.; Abel L.; Diamond M.S.; Cobat A.; Zhang S.-Y.; Casanova J.-L.; Borghesi A.. - In: THE JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 1540-9538. - ELETTRONICO. - 220:9(2023), pp. e20230661.1-e20230661.24. [10.1084/jem.20230661]
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.; Perez Lorenzo M.; Bizien L.; Achille C.; Trespidi F.; Burdino E.; Cassaniti I.; Lilleri D.; Fornara C.; Sammartino J.C.; Cereda D.; Marrocu C.; Piralla A.; Valsecchi C.; Ricagno S.; Cogo P.; Neth O.; Marin-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 M.R.; Rice C.M.; Rossini G.; Murray K.O.; Simonin Y.; Nagy A.; Barzon L.; Abel L.; Diamond M.S.; Cobat A.; Zhang S.-Y.; Casanova J.-L.; Borghesi A.
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