The puzzle of coeliac disease: pieces of the molecular pathogenesis

Abstract

Coeliac disease (CD) is a chronic intolerance to a dietary protein called gluten. This protein is present in common cereals such as wheat, barley and rye, and it is needed to prepare the derivate products such as bread or pasta. CD only occurs in individuals that carry certain altered genes. The identification of these genes and how they contribute to developing the disease is therefore crucial to understanding this disorder. When we started this study in 2001, we knew that gluten activated an abnormal immune response leading to specific intestinal damage. The work performed in this project aimed to identify which genes drive the development of the disease by comparing the expression of the genes in the intestine of coeliac patients to non-coeliacs. This work unraveled new insights into the adaptive and innate immune responses to gluten, and led us to propose that the damage in the intestine occurs because the intestinal cells are not able to reach their complete functionality and their location. The knowledge gained will guide the search for other genes that cause CD. It will also help the development of diagnostic tools for identifying patients at risk of developing CD and of new avenues for therapeutic intervention.