Children with autism spectrum disorders experiencing neuropsychiatric symptoms, cognitive skills, and gastrointestinal symptoms exhibit distinct innate immune abnormalities and transcriptional profiles in peripheral blood monocytes (47.7)

Abstract

Abstract ASD is considered a behavioral syndrome associated with multiple genetic and environmental factors. This study focuses on a subset of ASD children characterized by fluctuating behavioral symptoms and cognitive skills, triggered by immune insults, in addition to chronic GI symptoms (ASD-immune subtype; ASD-IS). The study included ASD-IS (N=19), control ASD (N=29), and normal control (N=26) children. We evaluated production of pro-inflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in response to agonists of toll like receptors (TLRs), polyclonal T cell stimulants, and recall antigens (Ags), and transcriptional profiles of PB monocytes. ASD-IS PBMCs produced less pro-inflammatory (IL-1β, IL-6, IL-12, and IL-23) and counter-regulatory (IL-10 and sTNFRII) cytokines with TLR agonists and less Th1 cytokines (IFN-γ and TNF-α) with recall Ags than control cells. ASD-IS PBMC also produced higher amounts of CCL2 than controls. Transcript profiles of ASD-IS monocytes were distinguished by altered mRNA expression (>2x) in >900 genes compared with either ASD or normal controls. Among these, 392 genes overlapped in the two control groups, including genes regulating TLR signaling, inflammatory responses, cell migration/adhesion, chemokines (CCL2 and CCL7), and genes associated with risks for autism, sychizophrenia, and depression. Our findings indicate a role of innate immunity in the puzzling clinical features observed in ASD-IS children.