title: Autoantibodies against neuronal progenitors in sera from children with autism.
abstract: The pathological role of autoantibodies in development of CNS disorders is a new idea with growing interest among neuroscientists. The involvement of autoimmune response in the pathogenesis of autism spectrum disorders (ASD) has been suggested by the presence of multiple brain-specific autoantibodies in children with ASD and in their mothers. The possibility of the effect of autoimmunity on neurogenesis and postnatal brain plasticity has not been determined. The presence of autoantibodies against human neuronal progenitor cells (NPCs) stimulated for neuronal differentiation in culture was tested in sera from children with autism (n=20) and age-matched controls (n=18) by immunoblotting and immunocytochemistry. Immunoreactivity against multiple NPCs proteins of molecular sizes of approximately 55 kDa, 105 kDa, 150 kDa, and 210 kDa in sera from individuals with autism had a higher incidence and was stronger than in control sera which immunoreacted mainly with a 150 kDa protein. The sera from children with autism immunoreacted the strongest with NPCs expressing neuronal markers Tuj1 and doublecortin, but not astrocyte marker GFAP. The epitopes recognized by antibodies from sera were not human-specific because they detected also NPCs in situ in murine hippocampus. The autoimmune reactions against NPCs suggest an impaired tolerance to neural antigens in autism. These autoantibodies may be symptomatic for autism and furthermore, their presence suggests that autoimmunity may affect postnatal neuronal plasticity particularly after impairment of blood-brain barrier. Future studies will determine the diagnostic value of the presence of autoantibodies in autism and the therapeutic value of prevention of autoimmunity in autism.
authors.affiliation: Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, USA. Electronic address: bozena.mazur-kolecka@opwdd.ny.us.
authors.forename: Bozena
authors.initials: B
authors.lastname: Mazur-Kolecka
authors.affiliation: Department of Psychology, NYS IBRDD, USA.
authors.forename: Ira L
authors.initials: IL
authors.lastname: Cohen
authors.affiliation: Department of Psychology, NYS IBRDD, USA.
authors.forename: Maripaz
authors.initials: M
authors.lastname: Gonzalez
authors.affiliation: Department of Human Genetics, NYS IBRDD, USA.
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Jenkins
authors.affiliation: Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, USA.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kaczmarski
authors.affiliation: Department of Human Genetics, NYS IBRDD, USA.
authors.forename: W Ted
authors.initials: WT
authors.lastname: Brown
authors.affiliation: Laboratory of Research Design and Analysis, NYS IBRDD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Flory
authors.affiliation: Department of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, USA.
authors.forename: Janusz
authors.initials: J
authors.lastname: Frackowiak
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D002478:Cells, Cultured; D002675:Child, Preschool; D000089622:Doublecortin Domain Proteins; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology*; D058953:Neural Stem Cells / Q000276:immunology*; D055495:Neurogenesis / Q000276:immunology*; D009479:Neuropeptides / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C498585:TUBB3 protein, human; D014404:Tubulin
keywords: Autism; Autoantibodies; Cell culture; Neurogenesis; Neuronal progenitor cells