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, TNFα), altered immunoglobulin levels, elevated complement proteins, and increased chemokine levels (CCL2, CCL5, CCL11) are reported in the plasma of young children with autistic disorder compared with matched typically developing children.
“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]
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.
“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]
Our results are in agreement with previous findings of elevated TNF-α expression in children with ASD and GI symptoms compared to non-inflamed controls that was similar to participants with Crohn's disease.
“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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- 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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