Innate Immunity Associated with Inflammatory Responses and Cytokine Production against Common Dietary Proteins in Patients with Autism Spectrum Disorder

Abstract

Objectives: Children with autism spectrum disorder (ASD) frequently reveal various gastrointestinal (GI) symptoms that may resolve with an elimination diet along with apparent improvement of some of the behavioral symptoms. Evidence suggests that ASD may be accompanied by aberrant (inflammatory) innate immune responses. This may predispose ASD children to sensitization to common dietary proteins (DP), leading to GI inflammation and aggravation of some behavioral symptoms. Methods: We measured IFN-γ, IL-5, and TNF-α production against representative DPs [gliadin, cow’s milk protein (CMP), and soy] by peripheral blood mononuclear cells (PBMCs) from ASD and control children [those with DP intolerance (DPI), ASD siblings, and healthy unrelated children]. We evaluated the results in association with proinflammatory and counter-regulatory cytokine production with endotoxin (LPS), a microbial product of intestinal flora and a surrogate stimulant for innate immune responses. Results: ASD PBMCs produced elevated IFN-γ and TNF-α, but not IL-5 with common DPs at high frequency as observed in DPI PBMCs. ASD PBMCs revealed increased proinflammatory cytokine responses with LPS at high frequency with positive correlation between proinflammatory cytokine production with LPS and IFN-γ and TNF-α production against DPs. Such correlation was less evident in DPI PBMCs. Conclusion: Immune reactivity to DPs may be associated with apparent DPI and GI inflammation in ASD children that may be partly associated with aberrant innate immune response against endotoxin, a product of the gut bacteria.

Immune Dysfunction in Autism: A Pathway to Treatment

“…Several studies have focused on immunological responses to dietary proteins, such as gluten and casein. Jyonouchi et al 57 found that peripheral blood mononuclear cells from children with ASD responded to gliadin, cow's milk protein, and soy by producing higher levels of inflammatory cytokines, compared with peripheral blood mononuclear cells from typically developing children. However, children in this study were selected on the basis of having previously seen behavior improvements on a restricted diet and may translate to a specific subgroup of ASD who have gastrointestinal (GI) symptoms.…”

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

“…It is possible that this indicates some abnormality of the gastrointestinal system, perhaps related to the immune abnormalities reported in the gastrointestinal tract in children with autism, that affects the apo. 29,31,64,65,66 Alternatively, the changes in apo could be due to differences in diet or various treatments.…”

Familial Autoimmune Thyroid Disease as a Risk Factor for Regression in Children with Autism Spectrum Disorder: A CPEA Study

“…There are reports that children with ASD have abnormalities in the peripheral blood cells and cytokines that mediate both innate and adaptive responses (Connolly et al, 1999;Croonenberghs, Bosmans, Deboutte, Kenis, & Maes, 2002a;Gupta, Aggarwal, Rashanravan, & Lee, 1998;Jyonouchi, Sun, & Itokazu, 2002;Singh, 1996;Warren, Foster, & Margaretten, 1987). Within the adaptive immune response, elevated levels have been reported for both T H 1 cytokines, commonly seen in autoimmune disorders (Singh, 1996), and T H 2 cytokines, as seen in atopic diseases (Gupta, Aggarwal, & Heads, 1998).…”