title: Aicardi-Goutières syndrome harbours abundant systemic and brain-reactive autoantibodies.
abstract: OBJECTIVE
  Aicardi-Goutières syndrome (AGS) is an autoimmune disorder that shares similarities with systemic lupus erythematous. AGS inflammatory responses specially target the cerebral white matter. However, it remains uncertain why the brain is the most affected organ, and little is known about the presence of autoantibodies in AGS. Here, we aim to profile specific autoantibodies in AGS and to determine whether these autoantibodies target cerebral epitopes.
  
  
  METHODS
  Using a multiplex microarray, we assessed the spectrum of serum autoantibodies in 56 genetically confirmed patients with AGS. We investigated the presence of immunoglobulins in AGS brain specimens using immunohistochemistry and studied the reactivity of sera against brain epitopes with proteomics.
  
  
  RESULTS
  Serum from patients exhibited high levels of IgGs against nuclear antigens (gP210, Nup62, PCNA, Ro/SSA, Sm/RNP complex, SS-A/SS-B), components of the basement membrane (entactin, laminin), fibrinogen IV and gliadin. Upon testing whether antibodies in AGS could be found in the central nervous system, IgGs were identified to target in vivo endothelial cells in vivo and astrocytes in brain sections of deceased patients with AGS. Using a proteomics approach, we were able to confirm that IgGs in serum samples from AGS patients bind epitopes present in the cerebral white matter.
  
  
  CONCLUSIONS
  Patients with AGS produce a broad spectrum of autoantibodies unique from other autoimmune diseases. Some of these autoantibodies target endothelial cells and astrocytes in the brain of the affected patients, perhaps explaining the prominence of neurological disease in the AGS phenotype.
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands Department of Experimental Immunology, Academic Medical Center, University of Amsterdam (UvA), Amsterdam, The Netherlands.
authors.forename: Eloy
authors.initials: E
authors.lastname: Cuadrado
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, USA.
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, USA.
authors.forename: Kristy J
authors.initials: KJ
authors.lastname: Brown
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Sandza
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, USA.
authors.forename: Asako
authors.initials: A
authors.lastname: Takanohashi
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam (UvA), Amsterdam, The Netherlands.
authors.forename: Machiel H
authors.initials: MH
authors.lastname: Jansen
authors.affiliation: Department of (Neuro)Pathology, SEIN-Stichting Epilepsie Instellingen Nederland, Academic Medical Center, University of Amsterdam (UvA), Amsterdam, The Netherlands.
authors.forename: Jasper
authors.initials: J
authors.lastname: Anink
authors.affiliation: Department of Neuropathology, Royal Victoria Hospital, Belfast, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Herron
authors.affiliation: Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Orcesi
authors.affiliation: Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Olivieri
authors.affiliation: Manchester Centre for Genomic Medicine, University of Manchester, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK.
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.affiliation: Department of (Neuro)Pathology, SEIN-Stichting Epilepsie Instellingen Nederland, Academic Medical Center, University of Amsterdam (UvA), Amsterdam, The Netherlands Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Hôpital Cochin, Université Paris Descartes, Service de Virologie, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.affiliation: Manchester Centre for Genomic Medicine, University of Manchester, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK.
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
authors.affiliation: Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam (UvA), Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000293:Adolescent; D000328:Adult; D001253:Astrocytes / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007223:Infant; D007231:Infant, Newborn; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008947:Mixed Connective Tissue Disease / Q000276:immunology; D009421:Nervous System Malformations / Q000235:genetics / Q000276:immunology*; D040901:Proteomics / Q000379:methods; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M
keywords: Autoantibodies; Autoimmune Diseases; Autoimmunity; Inflammation; Systemic Lupus Erythematosus