Abstract # 1787 Unique immune profiles in children with autism who experience gastrointestinal co-morbidity

Abstract

Children with an autism spectrum disorder (ASD) are 6–8 times more likely to have persistent gastrointestinal (GI) symptoms. In addition, intestinal and peripheral inflammation, altered microbiome profiles, and impaired intestinal permeability have also been observed in children with ASD who exhibit GI issues. To further assess immune dysfunction and relationship to behavior in children with ASD and GI co-morbidities, we analyzed samples from children placed into the following study groups based on responses from standardized GI questionnaires: children with ASD who experience GI symptoms (ASDGI), children with ASD without a history of GI symptoms (ASDNoGI), or typically developing (TD) children. Cytokine analysis of supernatants collected from stimulated peripheral blood mononuclear cells, revealed elevated innate immune responses from ASDNoGI including increased levels of IL-1alpha, IL-1beta and TNFalpha after stimulation with Toll-Like receptor (TLR)-4 ligands compared to TD. The ASDGI group produced increased levels of mucosa-relevant cytokines IL-5, IL-15 and IL-17 compared to ASDNoGI following TLR-4 stimulation. Interestingly, the production of regulatory cytokine, TGFbeta1, was decreased across all stimulatory conditions in ASDGI compared to either ASDNoGI or TD groups. Furthermore, ASDGI scored worse on the Aberrant Behaviors Checklist than ASDNoGI. Overall, data from this study found evidence of reduced regulatory cytokines and increased mucosa-related cytokines in ASDGI which suggest that children with ASD and GI symptoms have an imbalance between regulatory and inflammatory pathways.