Type I IFN autoantibodies in three of seven Europeans with life-threatening Usutu virus infection
Adrian Gervais, Paul Bastard, Lucy Bizien, Francesca Trespidi, Micol Angelini, Giada Rossini, Tiziana Lazzarotto, Fausto Baldanti, Francesca Rovida, Alessandro Ferrari, Alessandro Mancon, Davide Mileto, Irene Cassaniti, Francesca Conti, Jonas Schmidt-Chanasit, Dániel Cadar, David M. Florian, Alessandro Borghesi, Anne Puel, Céline Delifer, Pierre Tiberghien, Xavier de Lamballerie, Guillaume André Durand, Judith H. Aberle, Anna Nagy, Yannick Simonin, Aurélie Cobat, Shen-Ying Zhang, Jean-Laurent CasanovaWe previously reported that two of three patients with severe Usutu virus (USUV) disease carried circulating autoantibodies (auto-Abs) neutralizing type I IFNs (AAN-I-IFN). Here, we studied four additional patients, bringing the total number of European patients with life-threatening USUV infection to seven (Austria, n = 1; France, n = 1; Hungary, n = 4; Italy, n = 1). Three of these patients (all male, aged 43, 77, and 78 years, one French and two Hungarian) had blood auto-Abs neutralizing at least 10 ng/ml IFN-α2 and IFN-ω and at least 1 ng/ml IFN-β. They suffered from meningitis (n = 1), meningoencephalitis (n = 1), or myocarditis (n = 1). The other four patients were similar demographically and clinically but had no detectable AAN-I-IFN. No AAN-I-IFN were found in the 63 individuals with silent USUV infection tested (P = 6.4 × 10−4, Fisher’s exact test). These AAN-I-IFN increased the risk of life-threatening USUV disease by 98.8-fold (95% CI: 4.12–2,369; P = 0.0046, Firth’s bias–corrected logistic regression) and, thus, account for almost half the cases of life-threatening USUV infection in Europe.