While useful in screening for celiac disease in patients who still are consuming gluten, tests that measure serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) have low sensitivity in detecting persistent villous atrophy in patients with biopsy-confirmed celiac disease on gluten-free diets, a meta-analysis found (Gastroenterology 2017;153:689-701).

EMA IgA and tTG IgA were developed and validated as screening tests; however, in the absence of other noninvasive methods for monitoring intestinal mucosal health, their use for the latter is “pervasive and advocated by several gastroenterology societies,” according to the authors. The investigators conducted the meta-analysis to see what evidence there was for this practice.

In a literature review, the authors found 26 studies that met their inclusion criteria, including six, 15, and five involving tTG IgA assays, EMA IgA assays, or both tTG IgA and EMA IgA tests, respectively. Because many of these studies weren’t designed to answer the same question the investigators sought to answer, they developed a quality assessment score based on four domains and nine criteria such as time between biopsy and antibody testing and patient accounts of diets. They defined true positive results as positive antibody testing and villous atrophy by Marsh 3 histology classification—destructive lesions with flat mucosa. True negatives had negative antibody testing and intact villi.

Both assays had high specificity in patients with persistent villous atrophy; tTG IgA, 0.83 and EMA IgA, 0.91. However, they had low sensitivity for detecting patients with this condition, 0.50 in the case of tTG IgA, and 0.45 for EMA IgA. In contrast, the two tests have both high sensitivity and high specificity in untreated celiac disease.

The findings underscore the need for other “validated sensitive measures that predict mucosal recovery,” according to the authors. “In the absence of a non-invasive biomarker, follow-up duodenal biopsy remains the only appropriate test to assess mucosal recovery in children and adults with celiac disease.”