Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Abstract

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterised by impairments in communication, social interaction, and the presence of restrictive and repetitive behaviours. Over the past decade, most of the research in ASD has focused on the contribution of genetics, with the identification of a variety of different genes and mutations. However, the vast heterogeneity in clinical presentations associated with this disorder suggests that environmental factors may be involved, acting as a “second hit” in already genetically susceptible individuals. To this regard, emerging evidence points towards a role for maternal immune system dysfunctions. This literature review considered evidence from epidemiological studies and aimed to discuss the pathological relevance of the maternal immune system in ASD by looking at the proposed mechanisms by which it alters the prenatal environment. In particular, this review focuses on the effects of maternal immune activation (MIA) by looking at foetal brain-reactive antibodies, cytokines and the microbiome. Despite the arguments presented here that strongly implicate MIA in the pathophysiology of ASD, further research is needed to fully understand the precise mechanisms by which they alter brain structure and behaviour. Overall, this review has not only shown the importance of the maternal immune system as a risk factor for ASD, but more importantly, has highlighted new promising pathways to target for the discovery of novel therapeutic interventions for the treatment of such a life-changing disorder.