What blood tests help diagnose celiac disease?

Two to 3% of patients with celiac disease have selective IgA deficiency.² These patients often have falsely negative serum IgA assays (for EMA, tTG, and AGA), so IgG is a diagnostic alternative.^8,9 In a cross-sectional study, 100% of 20 untreated celiac disease patients with IgA deficiency had positive IgG tests for tTG, AGA, and EMA despite negative IgA tests for the same antibodies.⁹ Eleven patients with celiac disease and no IgA deficiency all had positive tTG, AGA, and EMA tests, whether testing for the IgA or IgG forms.

Despite the performance of the IgG assays in this study, only IgG AGA has performed well in larger studies. In a systematic review, IgG tTG and IgG EMA had specificities of 95% but sensitivities of only 40%.⁷ IgG AGA has similar sensitivity to the IgA assay—approximately 80%—with a slightly lower specificity of 80%. The discrepancy in the sensitivity of IgG tTG and IgG EMA between studies occurs because of differing antibody levels with variations in dietary gluten.^9,10 Therefore, testing for IgG tTG and IgG EMA should be reserved for patients with selective IgA deficiency.

Another notable limitation of using serologic markers to diagnose celiac disease is poor sensitivity in patients with mild disease.¹¹ Diagnosis in these patients may be particularly challenging. Patients with karyotype abnormalities and those with diabetes are also more likely to have false-negative serologic tests.²

Recommendations from others

The AGA recommends using serologic markers to screen patients with either non-specific symptoms or medical conditions that increase the risk of celiac disease.³ Patients whose clinical profile causes a high index of suspicion and negative IgA serologic markers should be tested for selective IgA deficiency. The AGA recommends relying on small intestinal biopsy for the final diagnosis.

Both the AGA and the North American Pediatric Society for Pediatric Gastroenterology state that tissue transglutaminase and endomysial antibodies are the most useful serologic tests. Antigliadin antibody tests are considered inferior in terms of diagnostic accuracy.