Autoantibodies to cerebellum in children with autism associate with behavior.
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.
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, United States.
Paula
P
Goines
Lori
L
Haapanen
Robert
R
Boyce
Paul
P
Duncanson
Daniel
D
Braunschweig
Lora
L
Delwiche
Robin
R
Hansen
Irva
I
Hertz-Picciotto
Paul
P
Ashwood
Judy
J
Van de Water
D001321:Autistic Disorder / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D002531:Cerebellum / Q000276:immunology* / Q000378:metabolism; D002652:Child Behavior / Q000502:physiology; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology; D005326:Fetal Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans
D001323:Autoantibodies; D005326:Fetal Proteins