JPBS

Objective: Genetic, epigenetic, and environmental factors such as infections have been proposed as potential causes of autism spectrum disorder (ASD). Searching for the molecular mechanism by which infections might contribute to the etiopathogenesis of ASD, we analyze here the hypothesis that immune responses to infectious agents may cross-react with human proteins that, when altered, relate to autistic neurodevelopmental spectrum disorders. Methods: Viral and human proteins were analyzed for peptide sharing using the Pir Peptide Match resource. Results: We find that: (i) an intense peptide overlap occurs between ASD–related viruses and ASD–related human proteins, and might underlie cross-reactivity scenarios following viral infections; (ii) viral peptide sharing also occurs with Y-linked proteins, in this way highlighting an additional potential cross-reactivity burden that would involve male subjects only; (iii) many shared peptides are also part of epitopes experimentally validated as immunopositive in the human host. Conclusion: This study offers a cohesive set of data that suggests a contribution of immune cross-reactivity to the genesis of ASD.

autism spectrum disorders; viral infections; peptide cross-reactivity; autism-related proteins; Y-linked proteins