title: Catalytic autoantibodies against myelin basic protein (MBP) isolated from serum of autistic children impair in vitro models of synaptic plasticity in rat hippocampus.
abstract: Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple proteins expressed in the brain. One such autoantibody targets myelin basic protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA classes in high titers, but no autoantibodies of the IgM class. IgA autoantibodies act as serine proteinases and degrade MBP in vitro. They also induce a decrease in long-term potentiation in the hippocampi of rats either perfused with or previously inoculated with this IgA. Because this class of autoantibody causes myelin sheath destruction in multiple sclerosis (MS), we hypothesized a similar pathological role for them in ASD.
authors.affiliation: Department of Biological Sciences, Laboratory of Environmental Neurotoxicology, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile; Department of Pathology, Duke University Medical Center, Durham, NC, USA. Electronic address: gonza002@mc.duke.edu.
authors.forename: Mario
authors.initials: M
authors.lastname: Gonzalez-Gronow
authors.affiliation: Department of Medicine, Clinical Hospital of the University of Chile, Chile.
authors.forename: Miguel
authors.initials: M
authors.lastname: Cuchacovich
authors.affiliation: Department of Psychiatry, Chilean Association of Parents with Autistic Children (ASPAUT), Chile.
authors.forename: Rina
authors.initials: R
authors.lastname: Francos
authors.affiliation: Faculty of Education, Universidad del Desarrollo, Santiago, Chile.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cuchacovich
authors.affiliation: Department of Child Surgery, Clinica Santa Maria, Santiago, Chile.
authors.forename: Angel
authors.initials: A
authors.lastname: Blanco
authors.affiliation: Department of Biological Sciences, Laboratory of Environmental Neurotoxicology, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Sandoval
authors.affiliation: Department of Biological Sciences, Laboratory of Environmental Neurotoxicology, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile.
authors.forename: Cristian Farias
authors.initials: CF
authors.lastname: Gomez
authors.affiliation: Department of Biological Sciences, Laboratory of Environmental Neurotoxicology, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Valenzuela
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Rupa
authors.initials: R
authors.lastname: Ray
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Salvatore V
authors.initials: SV
authors.lastname: Pizzo
mesh_terms: D000293:Adolescent; D000818:Animals; D001321:Autistic Disorder / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000187:drug effects / Q000494:pharmacology*; D066298:In Vitro Techniques; D007976:Leupeptins / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology*; D018408:Patch-Clamp Techniques; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007070:Immunoglobulin A; D007976:Leupeptins; D004676:Myelin Basic Protein; C032854:leupeptin
keywords: Autism; Autoimmunity; Myelin basic protein; Protease antibodies; Rat hippocampi; Synaptic plasticity