Rearrangement of Enterocyte Cytoskeletal Proteins in Coeliac Disease

Introduction: Coeliac disease is an immune mediated gluten sensitive enteropathy in genetically susceptible individuals resulting in small intestinal inflammation characterized by villous atrophy, crypt hyperplasia and increases in intraepithelial and lamina propria lymphocytes. Although it is well established that immune reactivity to gliadin takes place with the production of proinflammatory cytokines, it is not clear how damage to the small intestinal mucosa ensues.

Aims and Methods: We investigated the enterocyte cytoskeletal framework of microtubules, microfilaments, intermediate filaments and associated adhesion molecules for evidence of damage in coeliac disease. Immunofluorescent histochemical staining was performed on biopsy sections from 10 controls, 10 treated coeliacs and 10 untreated coeliacs for the cytoskeletal proteins actin, tubulin and cytokeratin and the adhesion molecule marker E-cadherin. Slides were examined using high resolution digital microphotography.

Results: Our findings demonstrate a distinct contrast between the study groups. In patients with untreated coeliac disease a marked rearrangement of the actin cytoskeleton together with a collapse of microtubule structure is observed in the coeliac lesion in comparison with normal subjects. This is associated with a shift from discrete staining of enterocyte cell membranes with clearly defined cell borders, towards discontinuous membranous staining accompanied by an internalization of both E-cadherin and cytokeratin. A degree of normalization is observed in treated coeliac patients proportionate to the level of histological recovery.

Conclusion: Evaluation of enterocyte cytoskeletal proteins and associated adhesion molecules may be a useful indicator of damaging events in coeliac mucosa, thus leading to a better understanding of the pathogenic processes involved.