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Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders

Jyonouchi H, Geng L, Ruby A +2 more2005The Journal of PediatricsJournal Article
10.1016/j.jpeds.2005.01.027PubMed
GastrointestinalImmune/Innate

Abstract

OBJECTIVE: To evaluate an association between cytokine production with common dietary proteins as a marker of non-allergic food hypersensitivity (NFH) and gastrointestinal (GI) symptoms in young children with autism spectrum disorders (ASD). STUDY DESIGN: Peripheral blood mononuclear cells (PBMCs) were obtained from 109 ASD children with or without GI symptoms (GI [+] ASD, N = 75 and GI (-) ASD, N = 34], from children with NFH (N = 15), and control subjects (N = 19). Diarrhea and constipation were the major GI symptoms. We measured production of type 1 T-helper cells (Th1), type 2 T-helper cells (Th2), and regulatory cytokines by PBMCs stimulated with whole cow's milk protein (CMP), its major components (casein, beta-lactoglobulin, and alpha-lactoalbumin), gliadin, and soy. RESULTS: PBMCs obtained from GI (+) ASD children produced more tumor necrosis factor-alpha (TNF-alpha)/interleukin-12 (IL-12) than those obtained from control subjects with CMP, beta-lactoglobulin, and alpha-lactoalbumin, irrespective of objective GI symptoms. They also produced more TNF-alpha with gliadin, which was more frequently observed in the group with loose stools. PBMCs obtained from GI (-) ASD children produced more TNF-alpha/IL-12 with CMP than those from control subjects, but not with beta-lactoglobulin, alpha-lactoalbumin, or gliadin. Cytokine production with casein and soy were unremarkable. CONCLUSION: A high prevalence of elevated TNF-alpha/IL-12 production by GI (+) ASD PBMCs with CMP and its major components indicates a role of NFH in GI symptoms observed in children with ASD.

Key Biomarkers

IL-12Th1 cytokinesTh2 cytokinesTNF-α

Symptom Clusters

ConstipationDiarrheaLoose stools

References (4)

  • Colonic CD8 and γδ T-cell infiltration with epithelial damage in children with autismThe Journal of Pediatrics · 2001
  • Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autismMolecular Psychiatry · 2002
  • Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathologyJournal of Clinical Immunology · 2003
  • Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regressionJournal of Neuroimmunology · 2001

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