Celiac Disease - NIH Consensus Development Program - National ...

for the IgG-based test, while specificity is higher. Based on a small number of studies, sensitivityand specificity for AGA can be improved using a combination of the IgG and IgA tests.EMA-IgA is both highly sensitive and specific. Most studies demonstrate EMAsensitivities in excess of 94 percent in children and 90 percent in adults with specificities above97 percent in both age groups. Studies comparing the use of human umbilical cord with monkeyesophagus as substrate for the EMA tests show no difference in their performance values.TTG-IgA is also highly sensitive and specific. Initial studies on TTG used guinea pigprotein as antigen while most recent studies have used human recombinant protein. In twocomparative studies, human-derived assays were shown to have improved sensitivity andspecificity over guinea pig-derived tests. (26,35) One study found TTG-IgA by RIA to be moresensitive than by ELISA but with identical specificity. (19) In general, TTG-IgA and EMA-IgAtests have similar sensitivity and specificity.ARA-IgA is less frequently used in clinical practice and fewer studies are available toassess the sensitivity and specificity of this test. One study demonstrated a sensitivity of only64 percent (8) while others have found higher figures (table 1).Selective IgA deficiency is more common in individuals with CD and occurs inapproximately 2 percent of those with the condition. IgA-based tests for AGA, EMA, and TTGare unable to identify individuals with IgA deficiency who require a biopsy to diagnose CD.AGA-IgG tests are most often used for this purpose but are poorly predictive for positivehistological findings. (37,38) IgG-based tests for EMA and TTG may be more accurate foridentifying symptomatic individuals with CD. Sensitivity and specificity of TTG-IgG innon-IgA-deficient individuals with CD range from 84–97 percent and 91–93 percent,respectively. (39–41) There was good concordance between TTG-IgG and EMA-IgG in one study. (39)Good comparative studies on the sensitivity and specificity of the serological tests indifferent ethnic populations are not available. A few studies have compared results betweenchildren and adults. One study suggested AGA tests were better for identifying children under 5years of age while EMA-IgA were better for those over 5 years of age. (1) Similarly, sensitivityand specificity for TTG-IgA was higher for adults (95 percent and 100 percent) than children(93 percent and 97 percent). (25) It is also possible that EMA-IgA is less reliable in children under2 years of age. (2)SummaryTTG-IgA (human recombinant) and EMA-IgA are the most sensitive and specificserological tests available for identifying individuals who require an intestinal biopsy for CDdiagnosis. Their accuracy in clinical practice may not be as good as that reported from theresearch setting. Therefore, a positive diagnosis of CD should not be made on the basis of aserological test alone without intestinal biopsy confirmation. Serological tests may be lessreliable in very young children. AGA tests are no longer recommended as a screening testbecause of the variable sensitivity and specificity associated with this test. There is no advantageto using a panel of tests incorporating AGA, EMA, and TTG antibodies over a single test usingEMA or TTG.28