Mechanisms of non-IgE mediated adverse reaction to common Dietary Proteins (DPs) in children with Autism Spectrum Disorders (ASD)

Abstract

Rationale We have reported elevated IFN-γ/TNF-α production by peripheral blood mononuclear cells (PBMCs) against cow's milk protein (CMP), soy, and gliadin in a substantial number of ASD children (Neuropsychobiology 46:76, 2002). IFN-γ/TNF-α production is partly regulated by IL-10 (negatively) and IL-12 (positively). Methods We examined IFN-γ, IL-5, TNF-α, IL-10 and IL-12 production by PBMCs against common DPs in 68 ASD children on a regular diet (Median age 5.4 yr): >50% of them had gastrointestinal symptoms. Controls include 11 children with DP intolerance (DPI) (Median age 2.5 yr), and 10 normal children (Median age 3.3 y). Results ASD and DPI PBMCs produced larger amounts of IFN-γ and TNF-α; against CMP and gliadin than controls (p<0.01). IL-12 production against CMP was higher in ASD PBMCs (p<0.01). IL-10 production by ASD, DPI, and control PBMCs were equivalent, resulting in higher TNFα/IL-10 ratio with CMP/gliadin in ASD and DPI PBMCs (p<0.01). IL-12/IL-10 ratios with CMP/gliadin were also higher in ASD PBMCs (p<0.01), but not in DPI cells. In 11/11 DPI children, TNF-α/IL-10 ratios with CMP and/or gliadin were >0.5 with excellent responses to the appropriate elimination diet. TNF-α/IL-10 ratios >0.5 with CMP and gliadin were found in 41/68 and 32/68 ASD children, respectively. In these children, the elimination diet based on immune reactivity helped resolve GI symptoms and attenuate autistic behaviors by parental report. Conclusions Disregulated production of inflammatory and counter-regulatory cytokines may be associated with non-IgE mediated adverse reaction to common DPs in some ASD children, indicating therapeutic significance of dietary interventions in these children.