Laboratory Testing for Celiac Disease: Clinical and Methodological Considerations

Celiac disease (CeD) has an estimated prevalence of 1%-3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth.CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations.

Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma.

Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.