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

  1. Adrian Gervais
  2. Francesca Trespidi
  3. Alessandro Ferrari
  4. Francesca Rovida
  5. Astrid Marchal
  6. Stefania Croce
  7. Irene Cassaniti
  8. Mattia Moratti
  9. Jennifer L. Uhrlaub
  10. David M. Florian
  11. Karin Stiasny
  12. Elisa Burdino
  13. Micol Angelini
  14. Lucy Bizien
  15. Daniele Lilleri
  16. Veronica Codullo
  17. Tal Freund
  18. Yael Paran
  19. Avi Gadoth
  20. Roni Biran
  21. Alessandro Mancon
  22. Camilla Lucca
  23. Stefania Vogiatzis
  24. Monia Pacenti
  25. Mélodie Aubart
  26. Marco Zecca
  27. Patrizia Comoli
  28. Maria Antonietta Avanzini
  29. Jacques Fellay
  30. Antonio Piralla
  31. Francesca Conti
  32. Alberto Dolci
  33. Luisa Barzon
  34. Valeria Ghisetti
  35. Tiziana Lazzarotto
  36. Danilo Cereda
  37. Alessandro Aiuti
  38. Emmanuelle Jouanguy
  39. Paul Bastard
  40. Margaret R. MacDonald
  41. Charles M. Rice
  42. Anne Puel
  43. Laurent Abel
  44. Giada Rossini
  45. Davide Mileto
  46. Yannick Simonin
  47. Anna Nagy
  48. David Hagin
  49. Kristy O. Murray
  50. Fausto Baldanti
  51. Judith H. Aberle
  52. Aurélie Cobat
  53. Shen-Ying Zhang
  54. Jean-Laurent Casanova
  55. Alessandro Borghesi

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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 auto-antibodies (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 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 −16 ) for auto-Abs neutralizing only 100 pg/mL IFN-α2 and/or IFN-ω to >2000 (OR=2218.4; 95% CI: 125.1-39337.7, p <10 −16 ) for auto-Abs neutralizing high concentrations of IFN-α2 and high or low concentrations of IFN-ω. Pre-existing autoantibodies neutralizing type I IFNs are therefore causal for WNV encephalitis in about 40% of patients.

Summary

In 13 cohorts of individuals with WNV infection, the risk of WNV encephalitis is increased 20 to >2,000 times by circulating auto-Abs neutralizing type I IFNs, depending on the concentration and combination of type I IFNs neutralized and patient age.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Benedikt Strunz

    Review 2: "Autoantibodies Neutralizing Type I IFNs in 40% of Patients with WNV Encephalitis in Seven New Cohorts"

    Reviewers suggested further clarification is needed regarding certain study populations such as the effect of including immunocompromised patients or how patients with neuroinvasive West Nile virus were identified.

  2. Rapid Reviews Infectious Diseases

    John Beckham, Jennifer Berger

    Review 1: "Autoantibodies Neutralizing Type I IFNs in 40% of Patients with WNV Encephalitis in Seven New Cohorts"

    Reviewers suggested further clarification is needed regarding certain study populations such as the effect of including immunocompromised patients or how patients with neuroinvasive West Nile virus were identified.

  4. Version published to 10.1101/2025.08.31.25334556 on medRxiv