title: Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism.
abstract: BACKGROUND
  Autism is a neurodevelopmental disorder characterized by impairments in social interaction and deficits in verbal and nonverbal communication, together with the presence of repetitive behaviors or a limited repertoire of activities and interests. The causes of autism are currently unclear. In a previous study, we determined that 21% of children with autism have plasma autoantibodies that are immunoreactive with a population of neurons in the cerebellum that appear to be Golgi cells, which are GABAergic interneurons.
  
  
  METHODS
  We have extended this analysis by examining plasma immunoreactivity in the remainder of the brain. To determine cell specificity, double-labeling studies that included one of the calcium-binding proteins that are commonly colocalized in GABAergic neurons (calbindin, parvalbumin or calretinin) were also carried out to determine which GABAergic neurons are immunoreactive. Coronal sections through the rostrocaudal extent of the macaque monkey brain were reacted with plasma from each of seven individuals with autism who had previously demonstrated positive Golgi cell staining, as well as six negative controls. In addition, brain sections from adult male mice were similarly examined.
  
  
  RESULTS
  In each case, specific staining was observed for neurons that had the morphological appearance of interneurons. By double-labeling sections with plasma and with antibodies directed against γ-aminobutyric acid (GABA), we determined that all autoantibody-positive neurons were GABAergic. However, not all GABAergic neurons were autoantibody-positive. Calbindin was colabeled in several of the autoantibody-labeled cells, while parvalbumin colabeling was less frequently observed. Autoantibody-positive cells rarely expressed calretinin. Sections from the mouse brain processed similarly to the primate sections also demonstrated immunoreactivity to interneurons distributed throughout the neocortex and many subcortical regions. Some cell populations stained in the primate (such as the Golgi neurons in the cerebellum) were not as robustly immunoreactive in the mouse brain.
  
  
  CONCLUSIONS
  These results suggest that the earlier report of autoantibody immunoreactivity to specific cells in the cerebellum extend to other regions of the brain. Further, these findings confirm the autoantibody-targeted cells to be a subpopulation of GABAergic interneurons. The potential impact of these autoantibodies on GABAergic disruption with respect to the etiology of autism is discussed herein.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, 451 Health Sciences Drive, Suite 6510 GBSF, Davis, CA 95616, USA.|NIEHS Center for Children's Environmental Health, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Sharifia
authors.initials: S
authors.lastname: Wills
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.|The M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, CA 95817 USA.
authors.forename: Christy C
authors.initials: CC
authors.lastname: Rossi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.|The M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, CA 95817 USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bennett
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.|The M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, CA 95817 USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Martinez-Cerdeño
authors.affiliation: Department of Medical Microbiology and Immunology, University of California at Davis, Davis, CA 95616, USA.|The M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, CA 95817 USA.|NIEHS Center for Children's Environmental Health, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Ashwood
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.|The M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, CA 95817 USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Amaral
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, 451 Health Sciences Drive, Suite 6510 GBSF, Davis, CA 95616, USA.|The M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, CA 95817 USA.|NIEHS Center for Children's Environmental Health, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Van de Water