Type I IFN autoantibodies in three of seven Europeans with life-threatening Usutu virus infection

We 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.

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Publication Details

Journal
Journal of Human Immunity
Published
2026-11-03
DOI
https://doi.org/10.70962/jhi.20260092
Primary Topic
Mosquito-borne diseases and control
Type
article
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article

Type I IFN autoantibodies in three of seven Europeans with life-threatening Usutu virus infection

Paul Bastard, Francesca Conti, Tiziana Lazzarotto, Céline Delifer et al.
Journal of Human Immunity
Mosquito-borne diseases and control
article

Type I IFN autoantibodies in three of seven Europeans with life-threatening Usutu virus infection

Paul Bastard, Francesca Conti, Tiziana Lazzarotto, Céline Delifer, Guillaume André Durand, Adrian Gervais, Pierre Tiberghien, David M. Florian, Aurélie Cobat, Dániel Cadar, Alessandro Ferrari, Micol Angelini, Judith Helene Aberle, Fausto Baldanti, Davide Mileto, Jean‐Laurent Casanova, Lucy Bizien, Yannick Simonin, Alessandro Mancon, Anne Puel, Giada Rossini, Xavier Nicolas de Lamballerie, Shen‐Ying Zhang, Alessandro Borghesi, Irene Cassaniti, Anna Nagy, Jonas Schmidt‐Chanasit, Francesca Trespidi, Francesca Rovida
article en

Abstract

We 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.

Journal of Human ImmunityVol. 3(1)
University of Geneva (CH), Howard Hughes Medical Institute (US), Inserm (FR), Universität Hamburg (DE), Aix-Marseille Université (FR), University of Pavia (IT), Sorbonne Université (FR), Luigi Sacco Hospital (IT), Assistance Publique – Hôpitaux de Paris (FR), GNA University (IN), National Public Health and Medical Officer Service (HU), University Hospital of Geneva (CH), Mother Hospital (IN), Établissement Français du Sang (FR), Policlinico San Matteo Fondazione (IT), Institut des Maladies Génétiques Imagine (FR), École Polytechnique Fédérale de Lausanne (CH), Geneva College (US), Medical University of Vienna (AT), Rockefeller University (US), University of Bologna (IT), Bernhard Nocht Institute for Tropical Medicine (DE)
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Mosquito-borne diseases and control
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