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. 2013 May:30:61-5.
doi: 10.1016/j.bbi.2013.01.084. Epub 2013 Feb 8.

Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder

Christine Wu Nordahl  1 , Daniel Braunschweig, Ana-Maria Iosif, Aaron Lee, Sally Rogers, Paul Ashwood, David G Amaral, Judy Van de Water
Affiliations

Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder

Christine Wu Nordahl et al. Brain Behav Immun. 2013 May.

Abstract

Autism spectrum disorder (ASD) is very heterogeneous and multiple subtypes and etiologies likely exist. The maternal immune system has been implicated in the pathogenesis of some forms of ASD. Previous studies have identified the presence of specific maternal IgG autoantibodies with reactivity to fetal brain proteins at 37 and 73kDa in up to 12% of mothers of children with ASD. The current study evaluates the presence of these autoantibodies in an independent cohort of mothers of 181 preschool-aged male children (131 ASD, 50 typically developing (TD) controls). We also investigated whether ASD children born to mothers with these autism-specific maternal IgG autoantibodies exhibit a distinct neural phenotype by evaluating total brain volume using structural magnetic resonance imaging (MRI). Of the 131 ASD children, 10 (7.6%) were born to mothers with the 37/73kDa IgG autoantibodies (ASD-IgG). The mothers of the remaining ASD children and all TD controls were negative for these paired autoantibodies. While both ASD groups exhibited abnormal brain enlargement that is commonly observed in this age range, the ASD-IgG group exhibited a more extreme 12.1% abnormal brain enlargement relative to the TD controls. In contrast, the remaining ASD children exhibited a smaller 4.4% abnormal brain enlargement relative to TD controls. Lobar and tissue type analyses revealed that the frontal lobe is selectively enlarged in the ASD-IgG group and that both gray and white matter are similarly affected. These results suggest that maternal autoantibodies associated with autism spectrum disorder may impact brain development leading to abnormal enlargement.

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Figures

Figure 1
Figure 1
Total cerebral volume in ASD males born to mothers with 37/73kDa IgG autoantibodies (ASD-IgG), ASD males born to mothers negative for the 37/73KDa IgG antibodies (ASD), and typically developing (TD) male controls. The box plots depict the median, 25th and 75th percentiles. The whiskers denote the 10th and 90th percentiles. Values above the 90th and below the 10th percentile are plotted as points. As a subgroup, the ASD-IgG group exhibits a more extreme brain enlargement relative to TD controls than the ASD group
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