ECTOPIC CLASS-II MAJOR HISTOCOMPATIBILITY ANTIGENS IN HIRSCHSPRUNGS-DISEASE AND NEURONAL INTESTINAL DYSPLASIA

Although the etiology of Hirschsprung's disease and neuronal intestinal dysplasia remains obscure, both have histological abnormalities involving ganglion cells and neuronal elements. Searching for a common pathway that may inhibit normal maturation of neurogenic precursors, we examined the possible role of an immune mechanism in the maldevelopment of the enteric neural network. Six patients with Hirschsprung's disease were studied by comparing biopsy specimens from diseased colon with ones taken from proximal ganglionic colon in the same patients. These were similarly compared with colonic biopsy specimens from patients studied with chronic constipation or bowel removed at the time of operation for other disorders. Biopsies were taken from four other patients with neuronal intestinal dysplasia. Each was examined by hematoxylin & eosin staining, acetylcholinesterase histochemistry, and immuno-histochemistry of major histocompatibility complex (MHC) class I and class II antigens. All rectal samples from Hirschsprung's disease patients exhibited elevated acetylcholinesterase histochemistry and absent ganglia to confirm the diagnosis. These findings were correlated with marked elevation of class II MHC in the aganglionic area, whereas the proximal normal ganglionic segments showed no elevation. Rectal biopsy specimens from patients with chronic constipation exhibited no such elevation. A similar elevation of class II MHC was detected in the mucosa and submucosa of all four patients with the rare neuronal intestinal dysplasia disorder whose diagnosis was confirmed by giant ganglia in Auerbach's plexuses, aberrant Meissner's ganglia in the lamina propria mucosa, and giant neurofibrils in the mucosa and submucosa. The correlation of elevated class II MHC in these two neuronal dysfunction disorders may indicate an underlying autoimmune mechanism as is seen in thyroiditis and insulin dependent diabetes mellitus. These observations confirm those found in a small number of Hirschsprung's disease patients reported earlier, and extend the observation to other neuronal dysfunction disorders. These findings provoke a reexamination of the etiology of Hirschsprung's disease and may predict alternate therapies. © 1992.