Possible drug targets for celiac disease

Abstract

Celiac disease (CD) is an intestinal disorder caused by an altered immune response against wheat gluten, a common dietary antigen, and related cereal proteins. Both CD4⁺ and CD8⁺ T cells have a role in inducing the intestinal damage, although recent studies have also pinpointed the involvement of the innate immune response in CD pathogenesis. So far, the only available treatment for CD is the strict avoidance of gluten in the diet, but the poor compliance and the associated complications demand alternative therapies. During the last decade, the knowledge of genetic, molecular and cellular mechanisms leading to CD pathogenesis made great progress. The improved understanding of gluten peptides activating either adaptive or innate immune response, of HLA restriction molecules, as well as of cytokines that mediate most of the inflammatory reactions, opens several new promising perspectives for therapeutic intervention. This review discusses both molecular and cellular strategies to treat CD, including the use of proteolytic enzymes active on gluten peptides, antibodies neutralising IL-15 and IFN-γ, drugs targeting HLA, regulatory cytokines and T cells.

Keywords::

• celiac disease
• gliadin
• HLA blocking molecule
• IL-10
• prolyl endopeptidase
• tissue transglutaminase