Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease

Matthijs Oyaert; Pieter Vermeersch; Gert De Hertogh; Martin Hiele; Nathalie Vandeputte; Ilse Hoffman; Xavier Bossuyt

doi:10.1515/cclm-2013-1099

Article

Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease

Matthijs Oyaert , Pieter Vermeersch , Gert De Hertogh , Martin Hiele , Nathalie Vandeputte , Ilse Hoffman and Xavier Bossuyt

Published/Copyright: February 19, 2015

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 53 Issue 10

Abstract

Background: The European Society for Pediatric Gastroenterology and Nutrition states that if IgA anti-tissue transglutaminase (tTG) exceeds 10 times the upper limit of normal (ULN), there is the possibility to diagnose celiac disease (CD) without duodenal biopsy, if supported by anti-endomysium testing and human leukocyte antigen (HLA) typing. We aimed to evaluate whether combining IgA tTG and IgG anti-deamidated gliadin peptide (DGP) antibody testing and taking into account the antibody levels improves clinical interpretation.

Methods: We calculated likelihood ratios for various test result combinations using data obtained from newly diagnosed CD patients (n=156) [13 children <2 years, 45 children between 2 and 16 years, and 98 adults (>16 years)] and 974 disease controls. All patients and controls underwent duodenal biopsy. IgA anti-tTG and IgG anti-DGP assays were from Thermo Fisher and Inova.

Results: Likelihood ratios for CD markedly increased with double positivity and increasing antibody levels of IgA anti-tTG and IgG anti-DGP. Patients with double positivity and high antibody levels (>3 times, >10 times ULN) had a high probability for having CD (likelihood ratio ≥649 for >3 times ULN and ∞ for >10 times ULN). The fraction of CD patients with double positivity and high antibody levels was 59%–67% (depending on the assay) for >3 ULN and 33%–36% (depending on the assay) for >10 ULN, respectively. This fraction was significantly higher in children with CD than in adults.

Conclusions: Combining IgG anti-DGP with IgA anti-tTG and defining thresholds for antibody levels improves the serologic diagnosis of CD.

Keywords: anti-deamidated gliadin; anti-tissue transglutaminase; celiac disease; likelihood ratio

Corresponding author: Xavier Bossuyt, MD, PhD, Laboratory Medicine, Immunology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium, Phone: +32 16 347009, Fax: +32 16 347931, E-mail: xavier.bossuyt@uzleuven.be; Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium ; and Department of Microbiology and Immunology, KU Leuven – University of Leuven, Leuven, Belgium

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Received: 2013-12-21

Accepted: 2015-1-9

Published Online: 2015-2-19

Published in Print: 2015-9-1

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https://doi.org/10.1515/cclm-2013-1099

Keywords for this article

anti-deamidated gliadin; anti-tissue transglutaminase; celiac disease; likelihood ratio