Effects of maternal autoantibody exposure at the cellular level: implications for the developing brain

Maternal autoimmunity during pregnancy can have significant impacts on fetal development. In the case of maternal autoantibody-related autism (MARA), autoantibodies (aABs) reactive to fetal brain proteins in the circulation of pregnant mothers have been strongly associated with an offspring autism diagnosis. Clinical studies have identified the protein targets for the MARA aABs as well as maternal aAB patterns that are more commonly observed in mothers of children with autism, but not in mothers of neurotypical children. Additionally, rodent studies show that gestational exposure to MARA aABs alters offspring brain development and behavior. How MARA aABs cause changes at the cellular level is an area of active investigation. In this review, we discuss the potential mechanisms by which MARA aABs interact with key neuronal and non-neuronal cells as well as their target autoantigens in the developing brain. Additionally, we highlight the potential impacts of these interactions on the developmental trajectories of targeted cells, resulting in an autism diagnosis.