Follow-up of pediatric celiac disease: value of antibodies in predicting mucosal healing, a prospective cohort study

Abstract

Background: In diagnosing celiac disease (CD), serological tests are highly valuable. However, their role in following up children with CD after prescription of a gluten-free diet is unclear. This study aimed to compare the performance of antibody tests in predicting small-intestinal mucosal status in diagnosis vs. follow-up of pediatric CD.

Methods: We conducted a prospective cohort study at a tertiary-care center. 148 children underwent esophohagogastroduodenoscopy with biopsies either for symptoms ± positive CD antibodies (group A; n = 95) or following up CD diagnosed ≥ 1 year before study enrollment (group B; n = 53). Using biopsy (Marsh ≥ 2) as the criterion standard, areas under ROC curves (AUCs) and likelihood-ratios were calculated to estimate the performance of antibody tests against tissue transglutaminase (TG2), deamidated gliadin peptide (DGP) and endomysium (EMA).

Results: AUCs were higher when tests were used for CD diagnosis vs. follow-up: 1 vs. 0.86 (P = 0.100) for TG2-IgA, 0.85 vs. 0.74 (P = 0.421) for TG2-IgG, 0.97 vs. 0.61 (P = 0.004) for DPG-IgA, and 0.99 vs. 0.88 (P = 0.053) for DPG-IgG, respectively. Empirical power was 85% for the DPG-IgA comparison, and on average 33% (range 13-43) for the non-significant comparisons. Among group B children, 88.7% showed mucosal healing (median 2.2 years after primary diagnosis). Only the negative likelihood-ratio of EMA was low enough (0.097) to effectively rule out persistent mucosal injury. However, out of 12 EMA-positive children with mucosal healing, 9 subsequently turned EMA-negative.

Conclusions: Among the CD antibodies examined, negative EMA most reliably predict mucosal healing. In general, however, antibody tests, especially DPG-IgA, are of limited value in predicting the mucosal status in the early years post-diagnosis but may be sufficient after a longer period of time.

Figure 1

Recruitment flow chart.

Figure 2

Areas under ROC curves (AUCs) of antibody tests used in diagnosing untreated coeliac disease vs. monitoring coeliac disease after prescription of a gluten-free diet. Significant results are marked with asterisks. Anti-TG2 IgA and -IgG, anti-tissue transglutaminase IgA and -IgG; EMA, anti-endomysial antibodies IgA; anti-DGP IgA and -IgG, anti-deamidated-gliadin-peptide IgA and -IgG.

Figure 3

ROC curves of the antibody tests examined. In case of anti-TG2 IgA and IgG as well as anti-DGP IgG non-significant differences of AUC between primary diagnosis (solid black line) and follow-up setting (dashed grey line) were found while in anti-DGP IgA (bottom left) significant AUC differences were detected. For illustrative purposes, optimal cut-off points (with minimal distance to the upper left corner) are designated using correspondingly coloured arrows. Circle segments illustrate that the cut-off points chosen are indeed optimal, the diagonal line in each plot represents the general case of a random guess. Perfect discrimination would result in an ROC curve touching the upper left corner (100% Sensitivity, 100% Specificity). AUC, area under the curve; anti-TG2, anti-tissue transglutaminase; anti-DGP, antibodies against deamidated gliadin peptides.

Figure 4

Comparison of histology results of group B at diagnosis (before study enrollment) with the results of re-biopsies taken during the study.