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

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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.

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Authors and Affiliations

  1. The Inflammatory Bowel Disease Study Group, Royal Free and University College Medical School, London, United Kingdom

    Paul Ashwood, Andrew Anthony & Andrew J. Wakefield

  2. Centre for Paediatric Gastroenterology, Royal Free and University College, Medical School, London, United Kingdom

    Paul Ashwood

  3. Department of Histopathology, Royal Free and University College Medical School, London, United Kingdom

    Andrew Anthony

  4. Centre for Paediatric Gastroenterology, Royal Free and University College, Medical School, London, United Kingdom

    Alicia A. Pellicer, Franco Torrente & John A. Walker-Smith

  5. Gaslini Institute, Genoa, Italy

    Franco Torrente

  6. The International Child Development Resource Center, Florida

    Andrew J. Wakefield

Authors
  1. Paul Ashwood
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  2. Andrew Anthony
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  3. Alicia A. Pellicer
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  4. Franco Torrente
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  5. John A. Walker-Smith
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  6. Andrew J. Wakefield
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Correspondence to Paul Ashwood.

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Ashwood, P., Anthony, A., Pellicer, A.A. et al. Intestinal Lymphocyte Populations in Children with Regressive Autism: Evidence for Extensive Mucosal Immunopathology. J Clin Immunol 23, 504–517 (2003). https://doi.org/10.1023/B:JOCI.0000010427.05143.bb

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  • DOI: https://doi.org/10.1023/B:JOCI.0000010427.05143.bb

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