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

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doi:10.1023/B:JOCI.0000010427.05143.bb

Journal of Clinical Immunology

23 (6): 504-517, November 2003

Copyright © 2003 Plenum Publishing Corporation

All rights reserved

Intestinal Lymphocyte Populations in Children with Regressive Autism:

Evidence for Extensive Mucosal Immunopathology

Ashwood

The Iflammatory Bowel Disease Study Group, Royal Free and University College

Medical School, London, united Kingdom. Centre for paediatrie

Gastroenterology, Royal Free and University college, Medical School, London,

United Kingdom; p.ashwood@...

Simon H. Murch

Centre for paediatrie Gastroenterology, Royal Free and University college,

Medical School, London, United Kingdom

The Iflammatory Bowel Disease Study Group, Royal Free and University College

Medical School, London, united Kingdom. Department of Histopathology, Royal

Free and University College Medical School, London, United Kingdom

A. Pellicer

Centre for paediatrie Gastroenterology, Royal Free and University college,

Medical School, London, United Kingdom

Franco Torrente

Centre for paediatrie Gastroenterology, Royal Free and University college,

Medical School, London, United Kingdom. Gaslini Institute, Genoa, Italy

A. Thomson

Centre for paediatrie Gastroenterology, Royal Free and University college,

Medical School, London, United Kingdom

A. -

Centre for paediatrie Gastroenterology, Royal Free and University college,

Medical School, London, United Kingdom

J. Wakefield

The Iflammatory Bowel Disease Study Group, Royal Free and University College

Medical School, London, united Kingdom. The International Child Development

Resource Center, Florida

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

Inflammation, mucosa, T lymphocyte, B lymphocyte, human

Article ID: 474304

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