Article

Journal of Clinical Immunology

, Volume 23, Issue 6, pp 504-517

First online:

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

  • Paul AshwoodAffiliated withThe Inflammatory Bowel Disease Study Group, Royal Free and University College Medical SchoolCentre for Paediatric Gastroenterology, Royal Free and University College, Medical School Email author 
  • , Andrew AnthonyAffiliated withThe Inflammatory Bowel Disease Study Group, Royal Free and University College Medical SchoolDepartment of Histopathology, Royal Free and University College Medical School
  • , Alicia A. PellicerAffiliated withCentre for Paediatric Gastroenterology, Royal Free and University College, Medical School
  • , Franco TorrenteAffiliated withCentre for Paediatric Gastroenterology, Royal Free and University College, Medical SchoolGaslini Institute
  • , John A. Walker-SmithAffiliated withCentre for Paediatric Gastroenterology, Royal Free and University College, Medical School
  • , Andrew J. WakefieldAffiliated withThe Inflammatory Bowel Disease Study Group, Royal Free and University College Medical SchoolThe International Child Development Resource Center

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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.

Inflammation mucosa T lymphocyte B lymphocyte human