Immunopathology of coeliac disease

Coeliac disease may be defined as a condition in which there is an abnormal jejunal mucosa with loss of villi, which improves morphologically after treatment with a gluten-free diet. Pathologically, there is damage to the jejunal enterocytes, with hyperplasia of crypt cells so that overall enteropoiesis is increased. On conventional or scanning electron microscopy the enterocytes are markedly abnormal. Histochemically, the normal punctate appearance of the lysosomes is lost and sensitive lysosomal enzyme assays on mucosal biopsy samples using isopycnic centrifugation techniques show that there is an increase in total lysosomal activity with reduction in lysosomal latency. Studies following gluten feeding in patients whose mucosa has returned to normal after treatment with a gluten-free diet show that pathological abnormalities appear within 4--8 hours of gluten challenge. Complement together with extracellular IgM can be demonstrated in the lamina propria, suggesting the formation of immune complexes. In untreated coeliac disease there is a significant reduction in serum levels of C3 and C4. There is also evidence indicating the presence of immune complexes in the serum. Coeliac disease may therefore be an intestinal model of an immune complex disease, in which an antigen derived from gluten reacts with an antibody formed locally in the gut, fixing complement and causing damage to the enterocyte by activation of lysosomes.