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The Adaptive Immune Response in Children with ASD Correlates with Behavior Severity
Objectives: To address the question of heterogeneity in immune responses, we sought to examine the diversity of immune profiles in young children with ASD and the association with behaviour. Moreover, to determine whether co-morbidity may affect immune response we sought to characterize peripheral T cell subsets in children with and without gastrointestinal (GI) symptoms compared to healthy typically developing children.
Methods: Peripheral blood mononuclear cells from children with ASD and from typically developing age-matched control subjects were stimulated with either lipopolysaccharide or phytohemagglutinin. Cytokine production was assessed after stimulation. Initially, the ASD study population was clustered into subgroups based on immune responses and assessed for behavioural outcomes. Secondly, we evaluated responses based on the presence or absence of GI symptoms.
Results: Children with ASD who had a proinflammatory profile based on lipopolysaccharide stimulation were more developmentally impaired as assessed by the Mullen Scales of Early Learning. They also had greater impairments in social affect as measured by the Autism Diagnostic Observation Schedule. These children also displayed more frequent sleep disturbances and episodes of aggression. Similarly, children with ASD and a more activated T cell cytokine profile after phytohemagglutinin stimulation were more developmentally impaired as measured by the Mullen Scales of Early Learning. Interestingly, children with ASD and GI symptoms displayed elevated TH17 populations, while children with ASD who did not experience GI symptoms showed increased frequency of TH2 populations. Both ASD groups showed evidence of reduced regulatory T cell populations compared to typically developing children.
Conclusions: Children with ASD may be phenotypically characterized based upon their immune profile. Those showing increased T cell activation/skewing display a more impaired behavioural profile than children with noninflamed or non-T cell activated immune profiles. These data also suggests that children with ASD may have deficits in immune regulation that leads to differential inflammatory T cell subsets. Overall, there may be several possible immune subphenotypes within the ASD population but that they commonly correlate with more severe behavioral impairments.