Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients.
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- Academic Journal
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- Gervais A; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Rovida F; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Avanzini MA; Laboratory of Pediatric Hemato-Oncology and Bone Marrow Transplantation, San Matteo Research Hospital , Pavia, Italy.; Croce S; UOSD Cell Factory, San Matteo Research Hospital , Pavia, Italy.; Marchal A; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Lin SC; Departments of Medicine, 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, St. Louis, MO, USA.; Ferrari A; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Thorball CW; Precision Medicine Unit, Lausanne University Hospital and University of Lausanne , Lausanne, Switzerland.; School of Life Sciences, Swiss Federal Institute of Technology , Lausanne, Switzerland.; Constant O; Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS , Montpellier, France.; Le Voyer T; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Philippot Q; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Rosain J; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris , Paris, France.; Angelini M; Neonatal Intensive Care Unit, San Matteo Research Hospital , Pavia, Italy.; Pérez Lorenzo M; 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 , Paris, France.; Bizien L; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Achille C; Neonatal Intensive Care Unit, San Matteo Research Hospital , Pavia, Italy.; Trespidi F; Neonatal Intensive Care Unit, San Matteo Research Hospital , Pavia, Italy.; Burdino E; Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, ASL Città di Torino , Turin, Italy.; Cassaniti I; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Lilleri D; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Fornara C; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Sammartino JC; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Cereda D; Direzione Generale Welfare , Lombardy, Italy.; Marrocu C; Department of Biomedical Sciences for Health, Postgraduate School of Public Health, University of Milan, Milan, Italy.; Piralla A; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Valsecchi C; Laboratory of Pediatric Hemato-Oncology and Bone Marrow Transplantation, San Matteo Research Hospital , Pavia, Italy.; Ricagno S; Department of Biosciences, University of Milan, Milan, Italy.; Institute of Molecular and Translational Cardiology, San Donato Hospital , Milan, Italy.; Cogo P; Department of Medicine (DAME), Division of Pediatrics, University of Udine, Udine, Italy.; Neth O; Inborn Errors of Immunity Laboratory, Biomedicine Institute in Seville (IBiS), University of Seville/CSIC, 'Red de Investigación Translacional en Infectología Pediátrica' , Seville, Spain.; Paediatric Infectious Diseases, Rheumatology and Immunology Unit, Virgen del Rocío University Hospital , Seville, Spain.; Marín-Cruz I; Paediatric Infectious Diseases, Rheumatology and Immunology Unit, Virgen del Rocío University Hospital , Seville, Spain.; Pacenti M; Microbiology and Virology Unit, Padova University Hospital , Padova, Italy.; Sinigaglia A; Department of Molecular Medicine, University of Padova, Padova, Italy.; Trevisan M; Department of Molecular Medicine, University of Padova, Padova, Italy.; Volpe A; Department of Molecular Medicine, University of Padova, Padova, Italy.; Marzollo A; Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital , Padova, Italy.; Conti F; Pediatric Unit, University Hospital of Bologna , Bologna, Italy.; Lazzarotto T; Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Department of Medical and Surgical Sciences, Section of Microbiology, University of Bologna, Bologna, Italy.; Pession A; Pediatric Unit, University Hospital of Bologna , Bologna, Italy.; Viale P; Infectious Diseases Unit, University Hospital of Bologna , Bologna, Italy.; Fellay J; Precision Medicine Unit, Lausanne University Hospital and University of Lausanne , Lausanne, Switzerland.; School of Life Sciences, Swiss Federal Institute of Technology , Lausanne, Switzerland.; Ghirardello S; Neonatal Intensive Care Unit, San Matteo Research Hospital , Pavia, Italy.; Aubart M; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; Pediatric Neurology Department, Necker-Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Ghisetti V; Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, ASL Città di Torino , Turin, Italy.; Aiuti A; Pediatric Immunohematology Unit, IRCCS San Raffaele Scientific Institute , Milan, Italy.; San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute , Milan, Italy.; Vita-Salute San Raffaele University , Milan, Italy.; Jouanguy E; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, NY, USA.; Bastard P; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, NY, USA.; Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistante Publique-Hôpitaux de Paris , Paris, France.; Percivalle E; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Baldanti F; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.; Microbiology and Virology Unit, San Matteo Research Hospital , Pavia, Italy.; Puel A; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, NY, USA.; MacDonald MR; Laboratory of Virology and Infectious Disease, The Rockefeller University , New York, NY, USA.; Rice CM; Laboratory of Virology and Infectious Disease, The Rockefeller University , New York, NY, USA.; Rossini G; Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Murray KO; Department of Pediatrics, Section of Pediatric Tropical Medicine, Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.; Simonin Y; Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS , Montpellier, France.; Nagy A; National Reference Laboratory for Viral Zoonoses, National Public Health Center , Budapest, Hungary.; Barzon L; Microbiology and Virology Unit, Padova University Hospital , Padova, Italy.; Department of Molecular Medicine, University of Padova, Padova, Italy.; Abel L; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, NY, USA.; Diamond MS; Departments of Medicine, 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, St. Louis, MO, USA.; Cobat A; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, NY, USA.; Zhang SY; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, NY, USA.; Casanova JL; 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 , Paris, France.; Paris Cité University, Imagine Institute , Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, NY, USA.; Howard Hughes Medical Institute , New York, NY, USA.; Department of Pediatrics, Necker Hospital for Sick Children, Paris, France.; Borghesi A; School of Life Sciences, Swiss Federal Institute of Technology , Lausanne, Switzerland.; Neonatal Intensive Care Unit, San Matteo Research Hospital , Pavia, Italy.
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- Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
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- English
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.
(© 2023 Gervais et al.)