Intestinal Lymphocyte Populations in Children with Regressive Autism: Evidence for Extensive Mucosal Immunopathology

Paul Ashwood, Andrew Anthony, Alicia A. Pellicer, Franco Torrente, John A. Walker-Smith, Andrew J. Wakefield

Research output: Contribution to journalArticle

126 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)504-517
Number of pages14
JournalJournal of Clinical Immunology
Volume23
Issue number6
DOIs
StatePublished - Nov 2003

Fingerprint

Autistic Disorder
Lymphocytes
Population
Biopsy
Flow Cytometry
Enterocolitis
Gluten-Free Diet
Control Groups
Caseins
Inflammatory Bowel Diseases
Eosinophils
Cognition
Mucous Membrane
B-Lymphocytes
Pathology
Diet

Keywords

  • B lymphocyte
  • Human
  • Inflammation
  • Mucosa
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Intestinal Lymphocyte Populations in Children with Regressive Autism : Evidence for Extensive Mucosal Immunopathology. / Ashwood, Paul; Anthony, Andrew; Pellicer, Alicia A.; Torrente, Franco; Walker-Smith, John A.; Wakefield, Andrew J.

In: Journal of Clinical Immunology, Vol. 23, No. 6, 11.2003, p. 504-517.

Research output: Contribution to journalArticle

Ashwood, Paul ; Anthony, Andrew ; Pellicer, Alicia A. ; Torrente, Franco ; Walker-Smith, John A. ; Wakefield, Andrew J. / Intestinal Lymphocyte Populations in Children with Regressive Autism : Evidence for Extensive Mucosal Immunopathology. In: Journal of Clinical Immunology. 2003 ; Vol. 23, No. 6. pp. 504-517.
@article{0d4d858cf35e4b9094fb3a9311f382f5,
title = "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.",
keywords = "B lymphocyte, Human, Inflammation, Mucosa, T lymphocyte",
author = "Paul Ashwood and Andrew Anthony and Pellicer, {Alicia A.} and Franco Torrente and Walker-Smith, {John A.} and Wakefield, {Andrew J.}",
year = "2003",
month = "11",
doi = "10.1023/B:JOCI.0000010427.05143.bb",
language = "English (US)",
volume = "23",
pages = "504--517",
journal = "Journal of Clinical Immunology",
issn = "0271-9142",
publisher = "Springer New York",
number = "6",

}

TY - JOUR

T1 - Intestinal Lymphocyte Populations in Children with Regressive Autism

T2 - Evidence for Extensive Mucosal Immunopathology

AU - Ashwood, Paul

AU - Anthony, Andrew

AU - Pellicer, Alicia A.

AU - Torrente, Franco

AU - Walker-Smith, John A.

AU - Wakefield, Andrew J.

PY - 2003/11

Y1 - 2003/11

N2 - 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.

AB - 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.

KW - B lymphocyte

KW - Human

KW - Inflammation

KW - Mucosa

KW - T lymphocyte

UR - http://www.scopus.com/inward/record.url?scp=0842330646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0842330646&partnerID=8YFLogxK

U2 - 10.1023/B:JOCI.0000010427.05143.bb

DO - 10.1023/B:JOCI.0000010427.05143.bb

M3 - Article

C2 - 15031638

AN - SCOPUS:0842330646

VL - 23

SP - 504

EP - 517

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

SN - 0271-9142

IS - 6

ER -