Our correspondents criticize the fact that we used serological data to estimate the prevalence of celiac disease without confirming the diagnosis by using histology or measuring endomysium antibodies (EMA). They suggest only to consider for celiac disease the 47 subjects with transglutaminase antibodies (tTG) concentrations that reach the 10-fold value of the cut-off. Such an approach would lead to a serious underestimate of the prevalence of celiac disease in an epidemiological study. This may be concluded from the data of the Swedish ETICS study (1, 2).
We used this study as a comparator because:
Like our own study, this is a population-based cross sectional study in children;
Subjects with tTG values above the cut-off (>5U/mL) underwent biopsy testing, as did those with high normal values (2–5 U/mL); and
A tTG test from the same manufacturer based on the same antigen was used (ELIA Celikey® tTG-IgA ELISA in the Swedish study and ELIA Celikey® tTG-IgA Immunocap in our cohort; Phadia, now ThermoFisher, Freiburg, Germany).
A total of 192 children met the criteria for biopsy testing, biopsy specimens were taken from 184, and celiac disease was confirmed in 153. Thirteen false positive results (tTG>5 U/mL with normal histology) were offset by 17 false negative results (tTG<5 U/mL in pathological histology findings) (1).
The specificity of the cut-off values of 5 U/mL and 4 U/mL was 99.8% and 99.6%. Additionally, measuring EMA would have increased the specificity only minimally. tTG values above the 10-fold of the normal value were present in only 47 of 153 children with biopsy-confirmed celiac disease.
The retrospective Canadian study reported by Gidrewicz et al. that was cited by Prof Henker indeed showed poorer specificity for tTG antibodies (manufacturers of the test: Euroimmun) (3). However, serological and histological findings were up to six months apart. We do not know how many children had already been put on a gluten-free or low-gluten diet before they underwent biopsy testing.
The cited European multicenter study also raises questions (4). tTG positivity in the two German adult cohorts was 1.4% and 0.5%. The proportion of EMA positivity in subjects positive for tTG varied between 0.14% and 0.9% across the seven cohorts under investigation. This unusually high variance may be due to the varying quality of serum specimens in the cohorts. Any epidemiological screening study of celiac disease will always be subject to limitations, as we discussed in our study. The comparison with the results of the Swedish study, however, supports our conclusions about the prevalence of celiac disease in children and adolescents in Germany. This conclusion was supported during the review process—hence the suggestion by one of the reviewers to include “prevalence of celiac disease” in our title.
Footnotes
Conflict of interest statement
Prof Koletzko has received lecture or consultancy fees from Euroimmun, ThermoFisher. R-Biopharm, and Schär. She is leading two international studies on celiac disease that are partly funded by Euroimmun, ThermoFisher, Inova, R-Biopharm, Nestle, and Schär.
References
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