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Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms
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.
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“Elevated plasma cytokine levels (IL-1β, IL-6, IL-12p40 and TNFα) [82–84], altered immunoglobulin levels [85, 86], elevated levels of complement proteins [87], and increased chemokine levels (CCL2, CCL5 and CCL11) [88] are reported in the plasma of young children with AD compared with matched typically developing children.”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [84]
In the citing paper
“Increased pro-inflammatory (TNF-α and IL-6) but decreased regulatory (IL-10) cytokine production in mucosal lamina propria and epithelial lymphocytes was observed in ASD children with GI symptoms compared to typically developing controls matched on GI symptoms [21, 22].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [22]
In the citing paper
“Our results are in agreement with previous findings of elevated TNF-α expression in children with ASD and GI symptoms [87] compared to non-inflamed controls that was similar to participants with Crohn’s disease [22].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [22]
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Metadata
- Authors
- Ashwood, P., & Wakefield, A. J.
- Affiliations
- University of California, Davis (US)
- Johnson Center for Child Health and Development (US)
- Corresponding author
- Ashwood, Paul
- ORCID
- Ashwood, Paul
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2006-04
- Volume
- 173
- Issue
- 1-2
- Pages
- 126-134
- ISSN
- 0165-5728 (ISSN-L)
- OpenAlex
- W2033012158
- Cited by
- 202
- References
- 41
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 10 · 2018: 15 · 2017: 8 · 2016: 9 · 2015: 5 · 2014: 12 · 2013: 6 · 2012: 19
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- autism spectrum disorder, gastrointestinal symptoms, CD3+ T cells, intracellular cytokines, TNF-α, interferon-gamma, IL-10, IL-4, Crohn's disease, children
- MeSH terms
- Autistic Disorder, Child, Flow Cytometry, Gastrointestinal Diseases, Humans, Intestinal Mucosa, T-Lymphocytes, Cytokines, CD3 Complex
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