Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients-Reference-Cited by-同舟云学术

Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients

Published:2023-06-22 Issue:9 Volume:220 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Gervais Adrian¹²^ORCID,Rovida Francesca³⁴^ORCID,Avanzini Maria Antonietta⁵^ORCID,Croce Stefania⁶^ORCID,Marchal Astrid¹²^ORCID,Lin Shih-Ching⁷^ORCID,Ferrari Alessandro⁴^ORCID,Thorball Christian W.⁸⁹^ORCID,Constant Orianne¹⁰^ORCID,Le Voyer Tom¹²^ORCID,Philippot Quentin¹²^ORCID,Rosain Jérémie¹²¹¹^ORCID,Angelini Micol¹²^ORCID,Pérez Lorenzo Malena¹^ORCID,Bizien Lucy¹²^ORCID,Achille Cristian¹²^ORCID,Trespidi Francesca¹²^ORCID,Burdino Elisa¹³^ORCID,Cassaniti Irene⁴^ORCID,Lilleri Daniele⁴^ORCID,Fornara Chiara⁴^ORCID,Sammartino José Camilla⁴^ORCID,Cereda Danilo¹⁴^ORCID,Marrocu Chiara¹⁵^ORCID,Piralla Antonio⁴^ORCID,Valsecchi Chiara⁵^ORCID,Ricagno Stefano¹⁶¹⁷^ORCID,Cogo Paola¹⁸^ORCID,Neth Olaf¹⁹²⁰^ORCID,Marín-Cruz Inés²⁰^ORCID,Pacenti Monia²¹^ORCID,Sinigaglia Alessandro²²^ORCID,Trevisan Marta²²^ORCID,Volpe Andrea²²^ORCID,Marzollo Antonio²³^ORCID,Conti Francesca²⁴^ORCID,Lazzarotto Tiziana²⁵²⁶^ORCID,Pession Andrea²⁴,Viale Pierluigi²⁷^ORCID,Fellay Jacques⁸⁹^ORCID,Ghirardello Stefano¹²^ORCID,Aubart Mélodie¹²²⁸^ORCID,Ghisetti Valeria¹³^ORCID,Aiuti Alessandro²⁹³⁰³¹^ORCID,Jouanguy Emmanuelle¹²³²^ORCID,Bastard Paul¹²³²³³^ORCID,Percivalle Elena⁴^ORCID,Baldanti Fausto³⁴^ORCID,Puel Anne¹²³²^ORCID,MacDonald Margaret R.³⁴^ORCID,Rice Charles M.³⁴^ORCID,Rossini Giada²⁵,Murray Kristy O.³⁵^ORCID,Simonin Yannick¹⁰^ORCID,Nagy Anna³⁶,Barzon Luisa²¹²²^ORCID,Abel Laurent¹²³²^ORCID,Diamond Michael S.⁷^ORCID,Cobat Aurélie¹²³²^ORCID,Zhang Shen-Ying¹²³²^ORCID,Casanova Jean-Laurent¹²³²³⁷³⁸^ORCID,Borghesi Alessandro⁹¹²^ORCID

Affiliation:

1. Laboratory 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 1 , Paris, France

2. Paris Cité University, Imagine Institute 2 , Paris, France

3. University of Pavia 3 Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, , Pavia, Italy

4. Microbiology and Virology Unit, San Matteo Research Hospital 4 , Pavia, Italy

5. Laboratory of Pediatric Hemato-Oncology and Bone Marrow Transplantation, San Matteo Research Hospital 5 , Pavia, Italy

6. UOSD Cell Factory, San Matteo Research Hospital 6 , Pavia, Italy

7. Molecular Microbiology, Pathology and Immunology, and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine 7 Departments of Medicine, , St. Louis, MO, USA

8. Precision Medicine Unit, Lausanne University Hospital and University of Lausanne 8 , Lausanne, Switzerland

9. School of Life Sciences, Swiss Federal Institute of Technology 9 , Lausanne, Switzerland

10. Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS 10 , Montpellier, France

11. Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris 11 , Paris, France

12. Neonatal Intensive Care Unit, San Matteo Research Hospital 12 , Pavia, Italy

13. Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, ASL Città di Torino 13 , Turin, Italy

14. Direzione Generale Welfare 14 , Lombardy, Italy

15. Postgraduate School of Public Health, University of Milan 15 Department of Biomedical Sciences for Health, , Milan, Italy

16. University of Milan 16 Department of Biosciences, , Milan, Italy

17. Institute of Molecular and Translational Cardiology, San Donato Hospital 17 , Milan, Italy

18. Division of Pediatrics, University of Udine 18 Department of Medicine (DAME), , Udine, Italy

19. Inborn Errors of Immunity Laboratory, Biomedicine Institute in Seville (IBiS), University of Seville/CSIC, “Red de Investigación Translacional en Infectología Pediátrica” 19 , Seville, Spain

20. Paediatric Infectious Diseases, Rheumatology and Immunology Unit, Virgen del Rocío University Hospital 20 , Seville, Spain

21. Microbiology and Virology Unit, Padova University Hospital 21 , Padova, Italy

22. University of Padova 22 Department of Molecular Medicine, , Padova, Italy

23. Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital 23 , Padova, Italy

24. Pediatric Unit, University Hospital of Bologna 24 , Bologna, Italy

25. 25Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

26. Section of Microbiology, University of Bologna 26 Department of Medical and Surgical Sciences, , Bologna, Italy

27. Infectious Diseases Unit, University Hospital of Bologna 27 , Bologna, Italy

28. Necker-Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris 28 Pediatric Neurology Department, , Paris, France

29. Pediatric Immunohematology Unit, IRCCS San Raffaele Scientific Institute 29 , Milan, Italy

30. San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute 30 , Milan, Italy

31. Vita-Salute San Raffaele University 31 , Milan, Italy

32. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University 32 , New York, NY, USA

33. Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistante Publique-Hôpitaux de Paris 33 , Paris, France

34. Laboratory of Virology and Infectious Disease, The Rockefeller University 34 , New York, NY, USA

35. Section of Pediatric Tropical Medicine, Center for Human Immunobiology, Baylor College of Medicine and Texas Children’s Hospital 35 Department of Pediatrics, , Houston, TX, USA

36. National Reference Laboratory for Viral Zoonoses, National Public Health Center 36 , Budapest, Hungary

37. Howard Hughes Medical Institute 37 , New York, NY, USA

38. Necker Hospital for Sick Children 38 Department of Pediatrics, , Paris, France

Abstract

Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0–24.0, P value <10–15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1–186.4, P value <10–15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.

Funder

Howard Hughes Medical Institute

Rockefeller University

St. Giles Foundation

National Institutes of Health

National Center for Advancing Translational Sciences

Georgia Clinical and Translational Science Alliance

Fisher Center for Alzheimer’s Research Foundation

Meyer Foundation

JPB Foundation

Agence Nationale de la Recherche

French Foundation for Medical Research