Celiac disease: Role of genetics and immunity and update on novel strategies for treatment

Celiac disease (CD) is one of the most common inflammatory diseases of the small intestine which causes abdominal pain, diarrhoea, malabsorption, weight loss, anorexia, and iron deficiency anaemia in humans. It is a human leukocyte antigen (HLA)-linked disorder that is triggered by the gluten and gliadin proteins from wheat and related cereals. The presence of other genetic factors such as HLA-DQ2 and HLA-DQ8 have also been identified for the generation of circulating autoantibodies to the enzyme transglutaminase (TG2). The TG2 enzyme deamidates the gluten peptides and increases their affinity for the HLA-DQ2 or HLA-DQ8, which in turn cause a more vigorous activation of CD4+ T-helper 1 (Th1) cells and trigger the immune response, and such immune cascade eventually leads to intestinal membrane damage and malabsorption. Generally, CD is managed by lifelong gluten-free diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Several pharmacological agents and alternative therapies for treating CD are currently under development and are in clinical trials, The purpose of this review is to highlight the complex involvement of genetics and immunity in CD and to focus on the novel strategies being used for developing adjunct and alternative therapies for the treatment of CD. Biomedical Reviews 2014; 25: 45-58.