Autoantibodies to cerebellum in children with autism associate with behavior

Brain Behav Immun. 2011 Mar;25(3):514-23. doi: 10.1016/j.bbi.2010.11.017. Epub 2010 Dec 4.

Abstract

Autism is a heterogeneous disorder with a poorly understood biological basis. Some children with autism harbor plasma autoantibodies that target brain proteins. Similarly, some mothers of children with autism produce antibodies specific to autism that target pairs of fetal brain proteins at 37/73 and 39/73 kDa. We explored the relationship between the presence of brain-specific autoantibodies and several behavioral characteristics of autism in 277 children with an autism spectrum disorder and 189 typically developing age-matched controls. Further, we used maternal autoantibody data to investigate potential familial relationships for the production of brain-directed autoantibodies. We demonstrated by Western blot that autoantibodies specific for a 45 kDa cerebellar protein in children were associated with a diagnosis of autism (p=0.017) while autoantibodies directed towards a 62 kDa protein were associated with the broader diagnosis of autism spectrum disorder (ASD) (p=0.043). Children with such autoantibodies had lower adaptive (p=0.0008) and cognitive function (p=0.005), as well as increased aberrant behaviors (p<0.05) compared to children without these antibodies. No correlation was noted for those mothers with the most specific pattern of anti-fetal brain autoantibodies and children with the autoantibodies to either the 45 or 62 kDa bands. Collectively, these data suggest that antibodies towards brain proteins in children are associated with lower adaptive and cognitive function as well as core behaviors associated with autism. It is unclear whether these antibodies have direct pathologic significance, or if they are merely a response to previous injury. Future studies are needed to determine the identities of the protein targets and explore their significance in autism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Autistic Disorder / immunology*
  • Autistic Disorder / metabolism
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Blotting, Western
  • Cerebellum / immunology*
  • Cerebellum / metabolism
  • Child Behavior / physiology
  • Child, Preschool
  • Cognition / physiology
  • Fetal Proteins / immunology*
  • Fetal Proteins / metabolism
  • Humans

Substances

  • Autoantibodies
  • Fetal Proteins