The pathogenesis of coeliac disease has been investigated by studying the response of small intestinal hydrolases in patients with coeliac disease subject to gluten challenge. Small intestinal biopsies taken before and two and a half hours after a gluten challenge in five patients with coeliac disease who had been maintained on a gluten free diet were examined by a combination of electron and light microscopy, organ culture, pulse chase biosynthetic labelling, SDS-PAGE and autoradiography. Before the challenge, the small intestinal biopsies showed nearly normal morphology. Two and a half hours after the challenge there was deterioration in villus architecture, distortion of microvillus structure, disorganisation of the intermicrovillus pit region, an increase in lysosome like bodies in the apical cytoplasm of the luminal enterocytes and pronounced hypertrophy of the rough endoplasmic reticulum of these cells. SDS-PAGE of small intestinal biopsies from four treated coeliac patients before gluten challenge revealed normal microvillus membrane and hydrolase composition. There was a generalised reduction but no specific alteration in the pattern of polypeptide synthesis in the mucosa of the small intestine in these subjects two and a half hours after the gluten challenge. These results suggest that the generalised reduction in small intestinal brush border enzymes in coeliac patients is not the primary pathogenetic mechanism and represents a secondary effect.
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