Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology
Abstract
Inflammatory intestinal pathology has been reported in children with regressive autism (affected children). Detailed analysis of intestinal biopsies in these children indicates a novel lymphocytic enterocolitis with autoimmune features; however, links with cognitive function remain unclear. To characterize further, the nature and extent of this disease we examined the mucosal infiltrate using flow cytometry. Duodenal, ileal, and colonic biopsies were obtained from 52 affected children, 25 histologically normal, and 54 histologically inflamed, developmentally normal controls. Epithelial and lamina propria lymphocyte populations were isolated and examined by multicolor flow cytometry. Adjacent biopsies were assessed by semiquantitative histopathology. At all sites, CD3(+) and CD3(+)CD8(+) IEL as well as CD3(+) LPL were significantly increased in affected children compared with developmentally normal noninflamed control groups (p<0.01) reaching levels similar to inflamed controls. In addition, two populations--CD3(+)CD4(+) IEL and LP CD19(+) B cells--were significantly increased in affected children compared with both noninflamed and inflamed control groups including IBD, at all sites examined (p<0.01). Histologically there was a prominent mucosal eosinophil infiltrate in affected children that was significantly lower in those on a gluten- and casein-free diet, although lymphocyte populations were not influenced by diet. The data provide further evidence of a pan-enteric mucosal immunopathology in children with regressive autism that is apparently distinct from other inflammatory bowel diseases.
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These immune imbalances represent a unique gastrointestinal immunopathology characterized by ileal nodular lymphoid hyperplasia and immune cell infiltration throughout the GI tract.
“These immune imbalances represent a unique gastrointestinal immunopathology that is characterized by ileal nodular lymphoid hyperplasia and immune cell infiltration throughout the GI tract [18].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [18]
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Self-citation
- Authors
- Ashwood, P., Anthony, A., Pellicer, A. A., Torrente, F., Walker-Smith, J. A., & Wakefield, A. J.
- Affiliations
- The Royal Free Hospital (GB)
- Corresponding author
- Ashwood, Paul
- Venue
- Journal of Clinical Immunology
- Published
- 2003-11
- Volume
- 23
- Issue
- 6
- Pages
- 504-517
- ISSN
- 0271-9142 (ISSN-L)
- 1573-2592
- OpenAlex
- W2036955930
- Cited by
- 197
- References
- 32
- Citations by year
- 2025: 5 · 2024: 7 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 12 · 2017: 5 · 2016: 2 · 2015: 10 · 2014: 11 · 2013: 18 · 2012: 10
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- regressive autism, intestinal lymphocytes, intraepithelial lymphocytes, lamina propria lymphocytes, CD19+ B cells, inflammatory bowel disease, duodenal biopsy
- MeSH terms
- Adolescent, Autistic Disorder, Biopsy, Child, Flow Cytometry, Humans, Intestinal Mucosa, Intestine, Small, Lymphocytes, Inflammatory Bowel Diseases, Lymphocyte Subsets
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