Biochemical changes in the small intestine during development of naturally acquired wheat-sensitive enteropathy of Irish Setters were investigated. To distinguish primary biochemical abnormalities from secondary effects of intestinal damage, progeny of affected dogs reared on a normal wheat-containing diet were compared with their own littermates reared on a cereal-free diet and with age-matched clinically normal Irish Setters fed the same wheat-containing diet. Peroral jejunal biopsy specimens were sequentially obtained between weaning and 1 year of age; specific activity and reorientating sucrose density-gradient distribution of organelle marker enzymes were determined. Major primary biochemical abnormalities were not detected in affected progeny. In affected dogs fed wheat, there was a selective, but secondary, loss of the brush border alkaline phosphatase and aminopeptidase N activities. This loss was associated with the development of partial villus atrophy, but represented a specific effect of dietary wheat on the brush border, not merely a nonspecific effect of mucosal damage, because other brush border enzymes, including disaccharidases, were not similarly affected. Increased soluble activities of lysosomal and peroxisomal marker enzymes late in the disease process may represent alterations in these 2 organelles as a secondary consequence of mucosal damage.

Morphologic changes in the small intestine were investigated during development of naturally acquired wheat-sensitive enteropathy in Irish Setters. To distinguish underlying morphologic abnormalities from non-specific effects of intestinal damage, progeny of affected dogs reared on a normal wheat-containing diet were compared with their own littermates reared on a cereal-free diet and with age-matched clinically normal Irish Setters fed the same wheat-containing diet. Peroral jejunal biopsy specimens were taken sequentially between 4 months and 1 year of age. At 4 months of age, there were no differences in villus height, comparing the 3 groups, but increased numbers of intraepithelial lymphocytes and goblet cells were already present in biopsy specimens from the affected Irish Setters fed wheat. Dietary wheat resulted in a progressive reduction in virus height in the jejunum of affected Irish Setters from 6 months onward. Underlying morphologic abnormalities were not found, and the characteristic morphologic changes of this enteropathy were secondary to the presence of dietary wheat. However, development of partial villus atrophy was preceded by increased numbers of intraepithelial lymphocytes and goblet cells.