Autism Studies and Related Medical Conditions, January 2009 - TACA

We determined innate and adaptive immune responses in children with
developmental regression and autism spectrum disorders (ASD, N=71),
developmentally normal siblings (N=23), and controls (N=17). With
lipopolysaccharide (LPS), a stimulant for innate immunity, peripheral blood
mononuclear cells (PBMCs) from 59/71 (83.1%) ASD patients produced >2 SD
above the control mean (CM) values of TNF-alpha, IL-1beta, and/or IL-6
produced by control PBMCs. ASD PBMCs produced higher levels of
proinflammatory/counter-regulatory cytokines without stimuli than controls. With
stimulants of phytohemagglutinin (PHA), tetanus, IL-12p70, and IL-18, PBMCs
from 47.9% to 60% of ASD patients produced >2 SD above the CM values of
TNF-alpha depending on stimulants. Our results indicate excessive innate
immune responses in a number of ASD children that may be most evident in
TNF-alpha production.
PMID: 11694332 [PubMed - indexed for MEDLINE]
Jyonouchi H, Sun S, Itokazu N. Innate immunity associated with inflammatory
responses and cytokine production against common dietary proteins in patients with
autism spectrum disorder. Neuropsychobiology. 2002;46(2):76-84.
Department of Pediatrics, University of Minnesota, Minneapolis, Minn, USA.
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-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. CONCLUSION: Immune reactivity to
DPs may be associated with apparent DPI and GI inflammation in ASD children
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