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

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

Gervais A,Trespidi F,Ferrari A,Rovida F,Marchal A,Croce S,Cassaniti I,Moratti M,Uhrlaub J,Florian D,Stiasny K,Burdino E,Angelini M,Bizien L,Lilleri D,Codullo V,Freund T,Paran Y,Gadoth A,Biran R,Mancon A,Lucca C,Vogiatzis S,Pacenti M,Aubart M,Zecca M,Comoli P,Avanzini M,Fellay J,Piralla A,Conti F,Dolci A,Barzon L,Ghisetti V,Lazzarotto T,Cereda D,Aiuti A,Jouanguy E,Bastard P,MacDonald M,Rice C,Puel A,Abel L,Rossini G,Mileto D,Simonin Y,Nagy A,Hagin D,Murray K,Baldanti F,Aberle J,Cobat A,Zhang S,Casanova J,Borghesi A

Source :

2026 Mar 13

Pmid / DOI:

41836040

Abstract

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) 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) 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.© 2026 Gervais et al.

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