Autoantibodies to Cerebellum IN Children with AUTISM Associate with Behavior

Background:  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 autoantibodies that target fetal brain proteins.  It is unknown whether the presence of brain-directed autoantibodies in children relates to specific behavioral traits, or if there is a familial relationship for autoantibody production.

Objectives:  Explore the relationship between the presence of brain-specific autoantibodies in children and several behavioral characteristics of autism.  Investigate potential familial relationships for the production of brain-directed autoantibodies using maternal autoantibody data

Methods:  The incidence of plasma antibodies directed towards Rhesus macaque cerebellum proteins was determined in children with autism (AU, n=207), the broader diagnosis of autism spectrum disorder (ASD, n=70), and typically developing age-matched controls (n=189) via Western blot.  Plasma from the respective mothers of the child subjects was previously analyzed using western blot for IgG reactivity to fetal brain proteins.  The presence of cerebellum-specific IgG was considered with respect to 1) the child’s diagnosis, 2) scores on the ADOS, ADI-R, Aberrant Behavior Checklist (ABC), the Vineland Adaptive Behavioral Scales (VABS), and the Mullen Scales of Early Learning (MSEL), and 3) to the occurrence of maternal anti-fetal brain IgG in their respective mothers.  

Results:  We demonstrated that autoantibodies specific for a 45kDa cerebellum protein in children were associated with a diagnosis of AU (p=0.017) while autoantibodies directed towards a 62kDa protein were associated with the broader diagnosis of 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.  In many cases, this was true regardless of the child’s diagnosis.  No correlation was noted for those mothers with the most autism-specific pattern of anti-fetal brain autoantibodies and children with the autoantibodies to either the 45 or 62 kDa proteins. 

Conclusions:  These data suggest that antibodies towards brain proteins in children are linked to lower adaptive and cognitive function as well as core behaviors associated with autism.  The presence of these antibodies may relate to certain behavioral features associated with the disorder rather than autism specifically.  It is unclear whether these antibodies have direct pathologic significance, or if they are merely a marker of a previous event.  Future studies are needed to determine the identities of the protein targets and explore their significance in autism.