DIVERGENT EFFECTS OF PBDE-47 ON T CELL IMMUNE RESPONSES IN AUTISTIC AND TYPICALLY DEVELOPING CHILDREN

Background: Current models suggest a role for both genes and the environment in the etiology of autism. There is evidence that immune dysregulation may be a clinical feature of ASD.

Objectives: To compare the potential differential effect of a common environmental polybrominated diphenylether, PBDE-47, on the immune response in children with ASD (n=19) and age-matched typically developing controls (TD, n=18).

Methods: Peripheral blood mononuclear cells (PBMC) were exposed ex vivo to either 100 nM or 500 nM PBDE47 for 4 hrs. PBMC were then challenged with the T cell mitogen, PHA. We measured both the proliferative response and cytokine production following stimulation. The data, analyzed by Wilcoxon rank tests, took into account both the magnitude of the response, and how many responses went up or down within a subject population.

Results: There was a significant increase in the proliferative response following PHA stimulation in the presence of 100 nM PBDE-47 for the ASD group compared to a reduction in the TD controls. When the cells were pre-incubated with PBDE-47 at 500 nM, the proliferative response was not affected in the TD controls but was significantly elevated in the ASD subjects (p< 0.05). Regarding cytokine production, exposure to 100 nM PBDE-47 resulted in significantly lower values for IL-6, MIP-1alpha and MIP-1beta in both the TD and ASD groups. The relative responses of the ASD and TD subjects diverged in the presence of 100 nM PBDE, with TD showing greater reductions in levels of the cytokine IL-12, and the chemokines MIP-1alpha and MIP-1beta.

Conclusions: This data suggests that in vitro exposure of PBMC to PBDE-47 affects cell proliferation and cytokine production in a pediatric population. Moreover, PBMC from the ASD subjects was differentially affected when compared to the TD controls suggesting evidence of a differential sensitivity to the environmental contaminant PBDE-47.