Clinical testing of gliadin fractions in coeliac patients

Since the toxic fraction of cereal flour which damages the small bowel mucosa of patients with coeliac disease has not been fully defined in vivo, we studied the effect of intraduodenal infusions of different doses of unfractionated gliadin and of alpha-, beta-, gamma- and omega-gliadin subfractions on the morphology of multiple jejunal biopsies taken from two patients with treated coeliac disease. A dose-response study with increasing quantities of unfractionated gliadin in one coeliac patient showed that 1000 mg produced marked damaged in serial jejunal biopsies taken 2-3 h after commencing the infusion and that the changes had almost completely disappeared 72 h later. alpha-, beta-, gamma- and omega-gliadin were prepared, checked for purity and investigated for toxicity in two coeliac patients. After an intraduodenal challenge with 1000 mg of the four gliadin subfractions these were shown to have induced damage in the mucosa of jejunal biopsies taken 6 h later. These observations confirm the results of studies in vitro, which suggest that not only alpha-but beta-, gamma- and omega-gliadin are enterotoxic in coeliac disease.