Anti Tissue Transglutaminase-A ELISA (Anti-tTg-A ELISA)

Gluten-sensitive enteropathy or celiac disease is characterized by atrophy of the small intestinal villi leading to a so-called flat mucosa. It is caused by a pathological intolerance to gliadin, the alcohol-soluble fraction of gluten in wheat, rye, and barley. As celiac disease is caused by the uptake of gluten, consequently a gluten-free diet cures the disease completely and thus has to be maintained for a lifetime. Renewed consumption of gliadin leads to a return of the symptoms. The disease is HLAassociated (>95% of patients have DQ2 enREFd by DQA1*0501 and DQB1*0201) and manifests at any age with a peak onset in early childhood, even in neonatals. The incidence rates range from 1 in 4000 to 1 in 300 in European countries.   Diagnosis of celiac disease is made by small intestinal biopsy (demonstrating flat mucosa) supported by serological markers. Antibodies against gliadin and anti-endomysial antibodies (EMA) are of major significance. They are detected so far by indirect immunofluorescence, which is restricted to subclass IgA only. The identification of tissue transglutaminase (tTG) as the major target antigen of EMA provided the opportunity of a more easy and reliable diagnosis of celiac disease. tTG is an enzyme that upon wounding is released from cells where it is thought to aid in tissue repair.   Anti-tTG antibodies show higher sensitivity and specificity than anti-gliadin antibodies. Furthermore,  they correlate tightly with the activity of the disease and thus are especially useful for diet monitoring. The cross-link of tTG with gliadin-specific peptides results in neoepitopes of tTG. As these neoepitopes are structurally closer to the physiological antigens, the new generation Anti-tTG-A ELISAtests show a markedly increased sensitivity and specificity. These epitopes show no cross-reactivities with gliadin.  The determination of IgG antibodies to tTG is the only available specific serology for those 2% to 5% of patients with IgA deficiency. A high number of subclinical cases have been detected by screening for anti-tTG, fostering the theory that the majority of celiac disease cases is undetected and untreated (Iceberg model).