Celiac Disease: what is new on disease pathogenesis and management.

Celiac Disease (CD) is a common and lifelong intolerance to wheat gluten and to related cereal proteins. CD is associated with a wide spectrum of clinical manifestations and, despite the diagnosis has been improved in the recent years, it still remains strongly under diagnosed. CD is a multifactorial disorder resulting from the interplay between environmental and genetics factors. Its pathogenesis has classically been attributed to the activation of lamina propria CD4+ Th1 cells specifically reacting to gluten derived peptides. Nevertheless, recent studies have revealed a more complex picture, showing that gluten is also able to activate the innate immune system and the CD8+ T cells, and possess a marked non immune-mediated toxicity. In addition, despite the finding that virtually all CD patients are HLA-DQ2 or -DQ8 positive, the encoding genes are considered necessary but not sufficient for disease development, and a growing number of studies suggested that other susceptibility genes are involved. Herein we provide an overview of the current knowledge about the immune and non immune mediated effects of dietary gluten that lead to the intestinal mucosa damage, and summarise the genetic factors predisposing to CD. Moreover, we discuss the key role of the deamidating activity of auto-antigen tissue transglutaminase and of a possible dysfunction of immune regulation in the celiac disease development. We finally discuss how the recent advances in CD pathogenesis can be useful for the design of new therapeutic intervention strategies, alternative to the life-long gluten exclusion from the diet.