Innate and adaptive immunity in celiac disease.
The current review is prompted by recent studies indicating that adaptive immunity could be sufficient to explain rapid onset symptoms as well as many chronic effects of gluten in celiac disease.Gluten re-exposure in treated celiac disease drives a coordinated systemic cytokine release response implicating T-cell activation within 2 h. Instead of direct effects of gluten on innate immunity, long lasting memory CD4+ T cells activated within 2 h of ingesting gluten or injecting purified gluten peptides now appear to be responsible for acute digestive symptoms. In addition, memory B cells and plasma cells specific for gluten and transglutaminase 2, rather than innate immune cells, are the preferred antigen-presenting cells for gluten in the gut. A variety of innate immune stimuli such as transient infections and local intestinal microbiome, not necessarily gluten itself, may contribute to disease initiation and transition to overt intestinal mucosal injury. Gluten-specific adaptive immunity in the gut and blood are now shown to be closely linked, and systemic cytokine release after gluten provides an additional explanation for extraintestinal manifestations of celiac disease.Clinical studies utilizing cytokines as new biomarkers for gluten immunity promise to improve understanding of clinical effects of gluten, accelerate therapeutics development, and augment diagnosis.