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Peer-reviewedCC BYJournal of human immunity

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

  • Adrian Gervais1,2
  • Paul Bastard1,2,3,4
  • Lucy Bizien1,2
  • Francesca Trespidi5,6
  • Micol Angelini5
  • Giada Rossini7
  • Tiziana Lazzarotto7,8
  • Fausto Baldanti9,10
  • Francesca Rovida9,10
  • Alessandro Ferrari9,11
  • Alessandro Mancon12
  • Davide Mileto12
17 more authors
  • Irene Cassaniti9,10
  • Francesca Conti13,14
  • Jonas Schmidt-Chanasit15,16
  • Dániel Cadar15,17
  • David M Florian18
  • Alessandro Borghesi5,6,19,20
  • Anne Puel1,2,3
  • Céline Delifer21
  • Pierre Tiberghien21
  • Xavier de Lamballerie22,23
  • Guillaume André Durand22,23
  • Judith H Aberle18
  • Anna Nagy24
  • Yannick Simonin25
  • Aurélie Cobat1,2,3
  • Shen-Ying Zhang1,2,3
  • Jean-Laurent Casanova1,2,3,4,26
26 affiliations
  1. 1Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de La Santé et de La Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, Paris, France.
  2. 2Paris Cité University, Imagine Institute , Paris, France.
  3. 3St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
  4. 4Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France.
  5. 5Host-Pathogen Interaction Group and Neonatal Intensive Care Unit, San Matteo Research Hospital (Fondazione IRCCS Policlinico San Matteo) , Pavia, Italy.
  6. 6School of Life Sciences, Swiss Federal Institute of Technology , Lausanne, Switzerland.
  7. 7Microbiology Unit, University Hospital of Bologna, Bologna, Italy.
  8. 8Section of Microbiology, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
  9. 9Microbiology and Virology Unit, San Matteo Research Hospital (Fondazione IRCCS Policlinico San Matteo), Pavia, Italy.
  10. 10Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
  11. 11Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.
  12. 12Laboratory of Clinical Microbiology, Virology and Bioemergencies, Luigi Sacco Hospital, Milan, Italy.
  13. 13Pediatric Unit, University Hospital of Bologna, Bologna, Italy.
  14. 14Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
  15. 15Department of Arbovirology and Entomology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  16. 16Faculty of Mathematics, Informatics and Natural Sciences, Universität Hamburg, Hamburg, Germany.
  17. 17Virus Metagenomics and Evolution, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
  18. 18Medical University of Vienna, Center for Virology , Vienna, Austria.
  19. 19Neonatal and Pediatric Intensive Care Unit, Mother, Child and Adolescent Department, Geneva University Hospitals, Geneva, Switzerland.
  20. 20Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland.
  21. 21Établissement Français du Sang , La Plaine Saint-Denis, France.
  22. 22National Reference Center for Arboviruses, National Institute of Health and Medical Research and French Armed Forces Biomedical Research Institute , Marseille, France.
  23. 23Unité des Virus Émergents, Aix-Marseille University, Corsica University, IRD 190-Inserm 1207-IRBA , Marseille, France.
  24. 24National Center for Public Health and Pharmacy , Budapest, Hungary.
  25. 25Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM , Montpellier, France.
  26. 26Howard Hughes Medical Institute , New York, NY, USA.
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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.

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Cite

BibTeXRIS
BibTeX
@article{gervais2026type,
  title = {{Type I IFN autoantibodies in three of seven Europeans with life-threatening Usutu virus infection.}},
  author = {Adrian Gervais and Paul Bastard and Lucy Bizien and Francesca Trespidi and Micol Angelini and Giada Rossini and Tiziana Lazzarotto and Fausto Baldanti and Francesca Rovida and Alessandro Ferrari and Alessandro Mancon and Davide Mileto and Irene Cassaniti and Francesca Conti and Jonas Schmidt-Chanasit and Dániel Cadar and David M Florian and Alessandro Borghesi and Anne Puel and Céline Delifer and Pierre Tiberghien and Xavier de Lamballerie and Guillaume André Durand and Judith H Aberle and Anna Nagy and Yannick Simonin and Aurélie Cobat and Shen-Ying Zhang and Jean-Laurent Casanova},
  journal = {Journal of human immunity},
  year = {2026},
  month = nov,
  doi = {10.70962/jhi.20260092},
  url = {https://europepmc.org/article/MED/42975317},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Type I IFN autoantibodies in three of seven Europeans with life-threatening Usutu virus infection.
AU  - Adrian Gervais
AU  - Paul Bastard
AU  - Lucy Bizien
AU  - Francesca Trespidi
AU  - Micol Angelini
AU  - Giada Rossini
AU  - Tiziana Lazzarotto
AU  - Fausto Baldanti
AU  - Francesca Rovida
AU  - Alessandro Ferrari
AU  - Alessandro Mancon
AU  - Davide Mileto
AU  - Irene Cassaniti
AU  - Francesca Conti
AU  - Jonas Schmidt-Chanasit
AU  - Dániel Cadar
AU  - David M Florian
AU  - Alessandro Borghesi
AU  - Anne Puel
AU  - Céline Delifer
AU  - Pierre Tiberghien
AU  - Xavier de Lamballerie
AU  - Guillaume André Durand
AU  - Judith H Aberle
AU  - Anna Nagy
AU  - Yannick Simonin
AU  - Aurélie Cobat
AU  - Shen-Ying Zhang
AU  - Jean-Laurent Casanova
PY  - 2026
DA  - 2026/11/03
JO  - Journal of human immunity
DO  - 10.70962/jhi.20260092
UR  - https://europepmc.org/article/MED/42975317
AB  - 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.
SN  - 3065-8993
ER  -