Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests

BACKGROUND The objective of this study was to compare celiac disease (CD)- specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of CD. METHODS This retrospective study included sera from 149 CD patients and 119 controls, all with intestinal biopsy. All samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium. RESULTS Tests for dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Positive (76% vs. 93%) and negative (72% vs. 83%) predictive values were also higher for dpgli than for ngli. Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P < 0.00001). A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00. Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01. CONCLUSION Antibody tests for dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium permitted diagnosis or exclusion of CD without intestinal biopsy in a high proportion of patients (78%). Jejunal biopsy would be necessary in patients with discordant antibody results (22%). With this two-step procedure, only patients with no CD-specific antibodies would be missed.