Transglutaminase 2-targeted autoantibodies in celiac disease: Pathogenetic players in addition to diagnostic tools?

Celiac disease comprises intolerance against dietary gluten present in wheat, rye and barley, and it belongs to the most common food-related life-long disorders in Western countries. Nowadays celiac disease is conceived as an autoimmune-mediated systemic disorder commonly presenting as enteropathy in genetically susceptible individuals. The most obvious feature distinguishing celiac disease from other small-intestinal enteropathies is the presence of autoantibodies against transglutaminase 2 (TG2) during a gluten-containing diet. The gluten-derived gliadin peptides and the self, TG2, have established and well-accepted role in celiac disease pathogenesis. TG2 is known to deamidate, and crosslink gluten-derived gliadin peptides to itself, thereby favoring disease progression. The celiac disease-specific TG2-targeted autoantibodies are deposited in the small-bowel mucosa as well as in other tissues, and interestingly, extraintestinal manifestations of the disease involving these particular tissues have been reported. As the TG2-targeted autoantibodies have experimentally been shown to modulate the function of different cell types in vitro similarly to what has been reported to occur in untreated celiac disease, they could constitute an important contribution to disease progression. In this review we discuss the role of TG2, the autoantigen and the autoantibodies targeted against it in the pathogenesis of celiac disease.