Maternal brain reactive antibodies profile in autism spectrum disorder: an update

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with multifactorial etiologies involving both genetic and environmental factors. In the past two decades it has become clear that in utero exposure to toxins, inflammation, microbiome, and antibodies (Abs), may play a role in the etiology of ASD. Maternal brain-reactive Abs, present in 10-20% of mothers of a child with ASD, pose a potential risk to the developing brain because they can gain access to the brain during gestation, altering brain development during a critical period. Different maternal anti-brain Abs have been associated with ASD and have been suggested to bind extracellular or intracellular neuronal antigens. Clinical data from various cohorts support the increase in prevalence of such maternal brain-reactive Abs in mothers of a child with ASD compared to mothers of a typically developing child. Animal models of both non-human primates and rodents have provided compelling evidence supporting a pathogenic role of these Abs. In this review we summarize the data from clinical and animal models addressing the role of pathogenic maternal Abs in ASD. We propose that maternal brain-reactive Abs are an overlooked and promising field of research, representing a modifiable risk factor that may account for up to 20% of cases of ASD. More studies are needed to better characterize the Abs that contribute to the risk of having a child with ASD, to understand whether we can we predict such cases of ASD, and to better pinpoint the antigenic specificity of these Abs and their mechanisms of pathogenicity.