Autoantibody and autism spectrum disorder: A systematic review

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1.7 % of US pediatric population, with a growing prevalence world-wide. Autoimmunity is one of potential pathogenic factors for ASD, which is attracting much attention and undergoing extensive investigations. For more than a decade, many groups have been studying the association between autoantibodies and ASD. Although several narrative reviews have been published on autoantibodies and ASD, no systematic review or meta-analysis has been performed. In this study, we conducted the first systematic review and evaluated available evidence for the association between ASD and major autoantibodies to identifiable antigens, together with a broader discussion of autoantibodies with no identifiable antigens. The goal is to examine studies of pediatric subjects specifically and overall, we found that children with ASD expressed trends of higher levels of antibodies reactive to folate receptor α autoantibody, anti-myelin basic protein antibodies, anti-myelin-associated glycoprotein antibodies, anti-ribosomal P protein antibodies, anti-endothelial cell antibodies, and anti-nuclear antibody, compared to healthy controls. However, the quality of evidence is low across the board because most studies were small and many did not include comparison controls. In addition, we were not able to perform a meta-analysis due to large between-study heterogeneity or lack of quantitative measures in most studies. Finally, we discussed future directions for the development of diagnostic guidelines and therapeutic targets for possible autoimmune-mediated ASD subtypes.