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Cited by 235Celiac Disease Research and ManagementWheat and Barley Genetics and PathologyEosinophilic Esophagitis

Tests for Serum Transglutaminase and Endomysial Antibodies Do Not Detect Most Patients With Celiac Disease and Persistent Villous Atrophy on Gluten-free Diets: a Meta-analysis

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Silvester, Jocelyn A., Kurada, Satya, Szwajcer, Andrea, Kelly, Ciarán P., Leffler, Daniel A., Duerksen, Donald R.·2017·Gastroenterology
DOI 10.1053/j.gastro.2017.05.015PMC PMC5738024
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Abstract

Background & aims Tests to measure serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) were developed to screen for celiac disease in patients consuming gluten. However, they are commonly used to monitor patients on a gluten-free diet (GFD). We conducted a meta-analysis 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 GFD. Methods We searched PUBMED, EMBASE, BIOSIS, SCOPUS, clinicaltrials.gov, Science Citation Index, and Cochrane Library databases through November 2016. Inclusion criteria were studies of subjects with biopsy-confirmed celiac disease, follow-up biopsies, and measurement of serum antibodies on a GFD, biopsy performed on subjects regardless of symptoms, or antibody test results. Our analysis excluded subjects with refractory celiac disease, undergoing gluten challenge, or consuming a prescribed oats-containing GFD. Tests were considered to have positive or negative findings based on manufacturer cut-off values. Villous atrophy was defined as a Marsh 3 lesion or villous height:crypt depth ratio below 3.0. We constructed forest plots to determine the sensitivity and specificity of detection for individual studies. For the meta-analysis, a bivariate random effects model was used to jointly model sensitivity and specificity. Results Our search identified 5408 unique citations. Following review of abstracts, 442 articles were reviewed in detail. Only 26 studies (6 of tTG assays, 15 of EMA assays, and 5 of tTG and EMA assays) met our inclusion criteria. The most common reason studies were excluded from our analysis was inability to cross-tabulate histologic and serologic findings. The 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, they detected villous atrophy with low levels of sensitivity: 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). The tests had similar levels of performance in pediatric and adult patients. Conclusions In a meta-analysis of patients with biopsy-confirmed celiac disease undergoing follow-up biopsy on a GFD, we found that tests for serum tTG IgA and EMA IgA levels had low sensitivity (below 50%) in detection of persistent villous atrophy. We need more-accurate non-invasive markers of mucosal damage in children and adults with celiac disease who are following a GFD.

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  • Normalization of serology is widely used during follow-up as a proxy for mucosal healing in children with high positive and negative predictive values.

    “Normalization of serology is widely used during follow-up as a proxy for mucosal healing in children with high positive and negative predictive values (21-23).”

    From ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. (2022) · cites this paper as [21]

    The Discussion (page unavailable) acknowledges that using antibody tests to guide follow-up is common, but says negative tests should not be interpreted as evidence of mucosal recovery. It states that follow-up biopsy, not serology, is the appropriate test for assessing mucosal recovery in children and adults. This contradicts the claim that normalized serology is a reliable proxy for healing with high predictive values. (LLM, conf=0.90)

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  • Negative TGA results do not correlate well with dietary compliance.

    “negative TGA results do not correlate well with dietary compliance (21, 54).”

    From ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. (2022) · cites this paper as [21]

  • IgA-TGA has low sensitivity in detection of persistent villous atrophy.

    “A recent meta-analysis concluded that IgA-TGA has low sensitivity in detection of persistent villous atrophy, but the authors did not specify the levels of antibodies (only positive or negative) (21).”

    From ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. (2022) · cites this paper as [21]

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Authors
Silvester, J. A., Kurada, S., Szwajcer, A., Kelly, C. P., Leffler, D. A., & Duerksen, D. R.
Affiliations
  • Boston Children's Hospital (US)
  • Beth Israel Deaconess Medical Center (US)
  • University of Manitoba (CA)
Corresponding author
Duerksen, Donald R.
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2017-09
Volume
153
Issue
3
Pages
689-701.e1
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2017.05.015
PMC
PMC5738024
OpenAlex
W2619612092
Cited by
235
References
66
Citations by year
2026: 28 · 2025: 25 · 2024: 22 · 2023: 27 · 2022: 33 · 2021: 31 · 2020: 33 · 2019: 16 · 2018: 14 · 2017: 5
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK 07760)
  • Canadian Association of Gastroenterology (T32 DK 07760)
  • Canadian Institutes of Health Research (T32 DK 07760)
  • National Institutes of Health (T32 DK 07760)
Topics
  • Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Wheat and Barley Genetics and Pathology
  • Health Sciences › Medicine › Surgery › Eosinophilic Esophagitis
Keywords
celiac disease, anti-tissue transglutaminase antibodies, anti-endomysial antibodies, gluten-free diet, serological screening, sensitivity and specificity, duodenal biopsy
MeSH terms
Protein Glutamine gamma Glutamyltransferase 2, Atrophy, Autoantibodies, Celiac Disease, Humans, Immunoglobulin A, Intestinal Mucosa, Transglutaminases, Sensitivity and Specificity, GTP-Binding Proteins

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