Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum Disorder: Current Knowledge and its Implications for Potential Therapeutics

Abstract

Several studies have found a correlation between the presence of circulating maternal autoantibodies and neuronal dysfunction in the neonate. Specifically, maternal anti-brain autoantibodies, which may access the fetal compartment during gestation, have been identified as one risk factor for developing Autism Spectrum Disorder (ASD). Studies by our laboratory elucidated seven neurodevelopmental proteins recognized by maternal autoantibodies, whose presence is associated with a diagnosis of maternal autoantibody related (MAR) autism in the child. While the specific process of anti-brain autoantibody generation is unclear and the detailed pathogenic mechanisms are currently unknown, identification of the maternal autoantibody targets increases the therapeutic possibilities. The potential therapies discussed in this review provide a framework for possible future medical interventions.

Biodistribution and toxicity of epitope‐functionalized dextran iron oxide nanoparticles in a pregnant murine model

“…These antibodies maliciously react with fetal brain proteins and result in maternal autoantibody related (MAR) autism (Fox‐Edmiston & Van de Water, ). Ostensibly, the removal of these pathological autoantibodies from maternal circulation may limit development of MAR autism in neonates (Fox‐Edmiston & Van de Water, ). Seminal results from our previous publication demonstrated capture of MAR autoantibodies from human serum in vitro by MAR peptide‐functionalized dextran iron oxide nanoparticles (DIONPs) (called SNAREs; [Systems for Nanoparticle‐based Autoantibody Reception and Entrapment]; Bolandparvaz, Harriman, Alvarez, et al, ).…”

Antibody mediated epitope mimicry in the pathogenesis of Zika virus related disease

“…Thus, the literature suggests that the developing CNS is exposed to maternal antibodies in the first two trimesters. There is precedent for autoimmune diseases caused by the transplacental passage of antibody, including pemphigus, myasthenia gravis, and lupus [61, 63]. In dengue infection, maternal antibodies transfer to the fetus, achieving a level determined by maternal antibody titer [64].…”

Autoimmunity, Autoantibodies, and Autism Spectrum Disorder

“…Several immunologic risk factors have been described including: genetic associations with immune-related genes(9–16), family history of autoimmune disease(15, 17–21), maternal inflammation and infection during pregnancy(22–27), and altered immune responses in the children, and are associated with increased impairments in core and associated features of ASD(28). More specific to this review, maternal anti-brain autoantibodies, which are thought to access the fetal compartment during gestation, have been identified as one risk factor for developing ASD and are proposed to contribute to early neurodevelopmental perturbations in the developing fetus(29–31). …”