Laurie Barclay, MD

NEW YORK (MedscapeWire) Apr 30 — A regressive type of autism described in the April issue of Molecular Psychiatry may have an autoimmune basis, either directly or indirectly from an autoimmune enteropathy.

"We report findings of a novel form of enteropathy in children with autism, characterized by lymphocytic infiltration, increased crypt cell proliferation and enterocyte numbers, with co-localization of IgG and complement C1q on the enterocyte basolateral membrane," write F. Torrente, from Royal Free and University College Medical School in London, United Kingdom, and colleagues.

This comparative histologic study examined children with a form of autism characterized by regression in the second year of life after apparently normal early development. Earlier reports of immunologic abnormalities and unexpected bowel pathology in autistic children have come from this subgroup of affected patients. In this study, the researchers compared duodenal biopsies from 25 autistic children of this type with those from 11 children with celiac disease, 5 with cerebral palsy and mental retardation, and 18 histologically normal controls.

Compared with the normal and cerebral palsy control patients, the autistic children had increased numbers of enterocytes and Paneth cells, increased lymphocyte infiltration in epithelium and lamina propria, and upregulated crypt cell proliferation. Compared with those with celiac disease, the autistic children had fewer intraepithelial lymphocytes and lamina propria cells and more lamina propria T-cell populations. In 23 of 25 autistic children, but in none of the other subjects, there was IgG deposition on the basolateral epithelial surface, co-localizing with complement C1q.

Although these findings support an autoimmune basis for the unexpected bowel abnormalities in children with autism, the authors question the relevance of these findings to the general autistic population, because these children had more obvious bowel symptoms than are typically reported.

Interestingly, however, some children with regressive autism respond to enteric therapy. The bowel changes could also reflect a genetic condition affecting several systems, with brain symptoms more obvious than gastrointestinal symptoms. Although further research is needed to clarify the role of the "gut-brain axis" in autism, autoimmune mechanisms may suggest avenues for future treatment.

"It is possible that in the future there will be such a concept as 'autoimmune autism' within the autism spectrum," J. Licinio and colleagues from the University of California, Los Angeles, write in an accompanying editorial. "Other biological alterations may be the hallmarks of distinct disorders that may emerge from within our current classification of autism."

Mol Psychiatry. 2002;7(4):375-382;329

Reviewed by Gary D. Vogin, MD