Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder.
OBJECTIVE
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-gamma, IL-5, and TNF-alpha 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-gamma and TNF-alpha, 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-gamma and TNF-alpha production against DPs. Such correlation was less evident in DPI PBMCs.


CONCLUSIONS
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.
Jyonouchi
Harumi
H
Department of Pediatrics, University of Minnesota, Minneapolis, Minn, USA.
Sun
Sining
S
Itokazu
Nanae
N
D000293:Adolescent; D001321:Autistic Disorder / Q000276:immunology* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D004044:Dietary Proteins / Q000009:adverse effects* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology*; D005903:Gliadin / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008894:Milk Proteins / Q000009:adverse effects / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D030262:Soybean Proteins / Q000009:adverse effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D004044:Dietary Proteins; D015848:Interleukin-5; D008070:Lipopolysaccharides; D008894:Milk Proteins; D030262:Soybean Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005903:Gliadin