Evaluation of differential autoantibody profiles in gut and brain tissues in children with Autism Spectrum Disorder (ASD)

Abstract Autoimmunity is a comorbidity often associated with autism spectrum disorder (ASD), and a better understanding of immune dysbiosis and autism is crucial to identify differential ASD phenotypes and develop better biomarkers. We aimed to study autoantibody (aAb) reactivity to gut and brain tissues to find aAb profiles in children with autism that could serve to identify ASD subpopulations with biomarker potential. Methods: We used plasma from typically developing children (TD; n=149) and children diagnosed with ASD (n=208). To assess aAb reactivity, we probed plasma brain and gut tissues by Western blot. Results: While we found reactivity against brain (28% ASD and 32% TD), and gut (15% ASD and 11% TD) in both groups, we observed reactivity to antigens in defined molecular weight ranges in the gut tissue recognized by aAbs from the ASD subjects and not the TD samples. Further, some individuals had aAb reactivity to both brain and gut (8.6% ASD and 8% TD). These data are consistent with our previous studies against cerebellum tissue, where we reported aAb reactivity in both groups (ASD and TD), but some autoantibodies were differentially reactive in the ASD population. Conclusion: We identified aAbs reactive to brain and gut antigens in both TD and ASD children, with differential recognition of plasma from children with ASD to proteins in the gut extract. We are currently working on identification of the differentially recognized proteins in the gut tissue. Further, we can link our findings to the clinical data of these children, including reported GI issues. Such aAbs have the potential to serve as predictors of a subgroup of ASD individuals or facilitate a better understanding of the different sub-phenotypes of ASD based on differential aAb profiles.