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

Autoantibodies to cerebellum in children with autism associate with behavior

Paula Goines  1 , Lori Haapanen, Robert Boyce, Paul Duncanson, Daniel Braunschweig, Lora Delwiche, Robin Hansen, Irva Hertz-Picciotto, Paul Ashwood, Judy Van de Water
Affiliations

Autoantibodies to cerebellum in children with autism associate with behavior

Paula Goines et al. Brain Behav Immun. 2011 Mar.

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.

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Figures

Figure 1
Figure 1. IgG directed towards a 45kDa cerebellum protein in children with autism (AU)
Examples of plasma IgG reactivity in children with AU positive for the 45kDa band (7 examples on the left) compared to typically developing (TD) control subjects (8 examples on the right). Each strip is representative of plasma from a single child subject and all samples were run simultaneously on one western blot.
Figure 2
Figure 2. IgG directed towards a 62kDa cerebellum protein in children with the broader diagnosis of autism spectrum disorder (ASD)
Examples of plasma IgG reactivity in children with ASD positive for the 62kDa band (9 examples on the left) compared to typically developing (TD) control subjects (9 examples on the right). Each strip is representative of plasma from a single child subject and all samples were run simultaneously on one western blot.
Figure 3
Figure 3. 45kDa and 62kDa cerebellum protein targets are conserved between human and monkey specimens
Representative blot comparing IgG reactivity towards human (H) and Rhesus macaque (M) cerebellum proteins. Plasma IgG reactivity towards human and monkey proteins is compared in two children positive for IgG specific to the 45kDa protein (left), one child positive for IgG specific to 62kDa protein (middle) and one typically developing (TD) control child (right). A secondary-only control is depicted on the far left against Rhesus macaque cerebellum. Sample number 2 reactive for the 45 kDa band is a positive control from the previous Wills et al study (Wills et al., 2009) demonstrating that the previously described 52 kDa band is in fact the same as the 45 kDa band described herein.
See this image and copyright information in PMC

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