Colonic CD8 and T-cell infiltration with epithelial damage in children with autism

Raoul I. Furlano MD, Andrew Anthony PhD, Richard Day PhD, Angela Brown, Louise McGarvey, Michael A. Thomson FRCPCH, Susan E. Davies MRCPath, Mark Berelowitz FRCPsych, Alastair Forbes FRCP, Andrew J. Wakefield FRCS, John A. Walker-Smith FRCP and Simon H. Murch FRCP

From the University Department of Paediatric Gastroenterology, the Inflammatory Bowel Diseases Study Group, the University Departments of Medicine and Histopathology, and the Department of Child and Adolescent Psychiatry, Royal Free and University College School of Medicine, London, United Kingdom; and the IBD Research Unit, St Mark's Hospital, Harrow, London, United Kingdom.

Revised 15 June 2000. Available online 9 May 2002.

Abstract
Objectives:
We have reported colitis with ileal lymphoid nodular hyperplasia (LNH) in children with regressive autism. The aims of this study were to characterize this lesion and determine whether LNH is specific for autism. Methods: Ileo-colonoscopy was performed in 21 consecutively evaluated children with autistic spectrum disorders and bowel symptoms. Blinded comparison was made with 8 children with histologically normal ileum and colon, 10 developmentally normal children with ileal LNH, 15 with Crohn's disease, and 14 with ulcerative colitis. Immunohistochemistry was performed for cell lineage and functional markers, and histochemistry was performed for glycosaminoglycans and basement membrane thickness. Results: Histology demonstrated lymphocytic colitis in the autistic children, less severe than classical inflammatory bowel disease. However, basement membrane thickness and mucosal cell density were significantly increased above those of all other groups including patients with inflammatory bowel disease. CD8+ density and intraepithelial lymphocyte numbers were higher than those in the Crohn's disease, LNH, and normal control groups; and CD3 and plasma cell density and crypt proliferation were higher than those in normal and LNH control groups. Epithelial, but not lamina propria, glycosaminoglycans were disrupted. However, the epithelium was HLA-DR-, suggesting a predominantly TH2 response. Interpretation: Immunohistochemistry confirms a distinct lymphocytic colitis in autistic spectrum disorders in which the epithelium appears particularly affected. This is consistent with increasing evidence for gut epithelial dysfunction in autism. (J Pediatr 2001;138:366-72)

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