The role of maternal autoantibody exposure in brain development and behavior in autism

By Matthew Bruce

July 27, 2022

The immune system has a distinct role in many bodily functions across the lifespan, extending well beyond its capacity to fend off infections. Indeed, substantial research suggests that immune cells and their molecules are important orchestrators in early development, tissue maintenance, and healthy aging. Unsurprisingly, given this broad influence, dysregulation of the immune system has been linked to a multitude of conditions, including neurodevelopmental disabilities such as autism 

Research in Judy Van de Water’s lab has focused on understanding the role of the immune system in autism to provide insight about the biological basis of this neurodevelopmental condition. One major finding from this work has been that nearly 20% of mothers with children on the spectrum also present with specific patterns of circulating antibodies to self-proteins, known as autoantibodies.  

A recent collaborative effort by MIND Institute Intellectual and Developmental Disabilities Research Center (IDDRC) investigators Judy Van de Water, Jill Silverman, and Jacqueline Crawley, as well as researchers from Canada and the United Kingdom, used an animal model to evaluate the effects of these maternal autoantibodies on offspring brain development. This study, published in July 2021 in the journal Molecular Psychiatry, found that mice exposed to autism-specific maternal autoantibodies during gestation displayed increased brain size, similar to that seen in autistic individuals born to mothers with these autoantibodies. It was also apparent that certain regions in the brain, such as the amygdala and white matter areas, were more affected by maternal autoantibody exposure than others. Finally, the differences in brain volume observed in mice also related to altered social and repetitive behaviors and affected male and female offspring differently. 

These results suggest that maternal autoantibodies have a direct impact on the way that the brain grows and develops, and that these changes may underlie the development of autism in a subset of individuals. Current efforts are focused on understanding how these autoantibodies lead to altered outcomes using a combination of approaches. These include looking at the molecular and cellular level using mRNA sequencing and cell culture techniques. The overarching goal of our research program is to enhance the ability for early intervention and implementation of services to improve the lives of affected individuals.  

 infographic alt text: describes how maternal autoantibodies (antibodies that react to the body's own cells as a threat) may impact fetal brain growth and development, leading to autism in some people.  About 20% of mothers of autistic children have a particular pattern of autoantibodies.  Studies done on mice showed that mice exposed to maternal antibodies showed altered brain growth and autistic-like traits