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  • Jefferson Adams

    Serum Tests No Good for Measuring Gluten Compliance in Celiac Disease Patients

    Jefferson Adams


    Reviewed and edited by a celiac disease expert.

      Serum tests are no good for detecting gluten compliance in celiac disease patients.


    Caption: Photo: CC--Max.Pixel

    Celiac.com 06/28/2017 - Tests to measure serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) were developed to screen for celiac disease in patients who are actively eating gluten.

    However, doctors often use them to monitor patients on a gluten-free diet. Now, making sure celiac patients are successfully following a gluten-free diet is important, as unconscious gluten ingestion can lead to complications over time. But how accurate are these tests for assessing gluten-free compliance in celiac patients?



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    A team of researchers recently set out to assess the sensitivity and specificity of tTG IgA and EMA IgA assays in identifying patients with celiac disease who have persistent villous atrophy despite a gluten-free diet. The research team included Jocelyn A. Silvester, Satya Kurada, Andrea Szwajcer, Ciarán P. Kelly, Daniel A. Leffler, and Donald R. Duerksen. They are variously affiliated with the Farncombe Family Digestive Health Research Institute and Division of Gastroenterology, and the Department of Pathology and Molecular Medicine and Department of Medicine, McMaster University, Hamilton, Ontario.

    To begin their meta-analysis, the team searched PUBMED, EMBASE, BIOSIS, SCOPUS, clinicaltrials.gov, Science Citation Index, and Cochrane Library databases through November 2016. They included studies of subjects with biopsy-confirmed celiac disease, follow-up biopsies and measurement of serum antibodies on a gluten-free diet, biopsy performed on subjects regardless of symptoms or antibody test results.

    Their analysis excluded patients with refractory celiac disease, undergoing gluten challenge, or consuming a prescribed oats-containing gluten-free diet. They determined positive or negative findings based on manufacturer cut-off values. They defined villous atrophy a Marsh 3 lesion or villous height:crypt depth ratio below 3.0.

    They constructed forest plots to determine the sensitivity and specificity of detection for individual studies. For their meta-analysis, they used a bivariate random effects model to determine both sensitivity and specificity.

    Their search of abstracts revealed 5,408 unique citations, which yielded 442 articles for detailed review. Those reviewed articles yielded just 26 studies that met the team’s inclusion criteria (6 of tTG assays, 15 of EMA assays, and 5 of tTG and EMA assays). Inability to cross-tabulate histologic and serologic findings was the most common reason the team excluded a given study from analysis.

    They found that serum assays identified patients with persistent villous atrophy with high levels of specificity: 0.83 for the tTG IgA assay (95% CI, 0.79–0.87) and 0.91 for the EMA IgA assay (95% CI, 0.87–0.94).

    However, the tests showed low sensitivity for detecting villous atrophy: 0.50 for the tTG IgA assay (95% CI, 0.41–0.60) and 0.45 for the EMA IgA assay (95% CI, 0.34-0.57). Results were similar in both pediatric and adult patients.

    A meta-analysis of biopsy-confirmed celiac patients who received follow-up biopsy while on a gluten-free diet, showed that tests for serum tTG IgA and EMA IgA had low sensitivity, detecting persistent villous atrophy less than 50 percent of the time.

    The team supports the search for more accurate, non-invasive, markers of mucosal damage in celiac patients who follow a gluten-free diet.

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  • About Me

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,500 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

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