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Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms

Ashwood P, Wakefield AJ2006Journal of NeuroimmunologyJournal Article
10.1016/j.jneuroim.2005.12.007PubMed
GastrointestinalImmune/InnateNeurological

Abstract

Gastrointestinal pathology, characterized by lymphoid nodular hyperplasia and entero-colitis, has been demonstrated in a cohort of children with autistic spectrum disorder (ASD). Systemic and intestinal mucosal immune dysregulation was assessed in ASD children with gastrointestinal (GI) symptoms (n = 18), and typically developing controls (n = 27), including non-inflamed controls (NIC) and inflamed GI control children with Crohn's disease (CD), by analysis of intracellular cytokines in CD3+ lymphocytes. In both peripheral blood and mucosa, CD3+ TNFalpha+ and CD3+ IFNgamma+ were increased in ASD children compared with NIC (p < 0.004) and reached levels similar to CD. In contrast, peripheral and mucosal CD3+ IL-10+ were markedly lower in ASD children with GI symptoms compared with both NIC and CD controls (p < 0.02). In addition, mucosal CD3+ IL-4+ cells were increased (p < 0.007) in ASD compared with NIC. There is a unique pattern of peripheral blood and mucosal CD3+ lymphocytes intracellular cytokines, which is consistent with significant immune dysregulation, in this ASD cohort.

Key Biomarkers

CD3+ IFNgamma+CD3+ IL-10+CD3+ IL-4+CD3+ TNFalpha+Entero-colitisLymphoid nodular hyperplasia

Symptom Clusters

Autism spectrum disorder with GI symptomsGastrointestinal pathologyImmune dysregulation

References (8)

  • Colonic CD8 and γδ T-cell infiltration with epithelial damage in children with autismThe Journal of Pediatrics · 2001
  • Spontaneous Mucosal Lymphocyte Cytokine Profiles in Children with Autism and Gastrointestinal Symptoms: Mucosal Immune Activation and Reduced Counter Regulatory Interleukin-10Journal of Clinical Immunology · 2004
  • Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autismMolecular Psychiatry · 2002
  • Cytokines and brain function: relevance to interferon-alpha-induced mood and cognitive changesPubMed · 1998
  • 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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