Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients
Adrian Gervais, Astrid Marchal, Andrea Fořtová, Michaela Beránková, Lenka Krbková, Martina Pýchová, Jiřı́ Salát, Shuxiang Zhao, Nacim Kerrouche, Tom Le Voyer, Karin Stiasny, Simon Raffl, Anne Pachart, Samira Fafi‐Kremer, Simon Gravier, Davide F. Robbiani, Laurent Abel, Margaret R. MacDonald, Charles M. Rice, Gaia Weissmann, Tarek Kamal Eldin, Eva Robatscher, Elke Erne, Elisabetta Pagani, A. Borghesi, Anne Puel, Paul Bastard, Aurélie Velay, M. Martinot, Yves Hansmann, Judith H. Aberle, Daniel Růžek, Aurélie Cobat, Shen‐Ying Zhang, Jean‐Laurent Casanova
Abstract
Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.