Trend of Antitissue Transglutaminase Antibody Normalization in Children With Celiac Disease Started on Gluten‐free Diet

Abstract

Background: The aim of this study is to compare the performance of antitissue transglutaminase (atTG) chemiluminescence immunoassay (CLIA) with the standard enzyme-linked immunosorbent assay (ELISA) methods in monitoring celiac children after the start of gluten-free diet (GFD). Methods: Celiac children diagnosed between 2005 and 2016 at our centre were classified into 2 groups based on serum assay (ELISA vs CLIA) used for atTG monitoring, and were compared on percentage of decrease and time to normalization of atTG on GFD. Results: Among 260 included children, the rate of normalization of atTG levels at 30 months’ follow-up was 86% and 70% in ELISA and CLIA group, respectively (P < 0.01). Median time to normalization was 11.7 and 14.7 months in ELISA and CLIA group respectively (P = 0.003). Marsh score at diagnosis was not associated with time to atTG normalization (P = 0.770), whereas older age at diagnosis and higher baseline atTG predicted longer time to atTG normalization (P = 0.01, P < 0.01). Conclusions: The percentage and the time of the atTG normalization in celiac children on GFD should be interpreted according to the utilized assay: at 30 months’ follow-up children tested by CLIA are less likely to normalize atTG levels compared to those tested by ELISA. Younger age at diagnosis and lower baseline atTG are predictors of earlier atTG normalization, regardless of the adopted assay.

ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease

“…For decades, the most widely used CD serology assessment method has been ELISA and the majority of clinical evidence available has been addressed by this technique. Persistent positivity of chemiluminescence IgA-TGA should be interpreted with caution since it has a slower decrease over time (26) and should be better integrated with ELISA assay since more follow-up data are available on this latter technique with regards to dietary monitoring. Nevertheless, it should be clear that CD-specific antibody measurement does not suffice to evaluate compliance to a GFD and to establish complete recovery of mucosal healing.…”

“…However, TGA levels remained above 1× the upper level of normal (ULN) in 83.8% and above 10× ULN in 26.6% of studied children after 3 months on GFD (24). Full normalization of both TGA levels and histopathology may take over 2 years, particularly in those with severe small-bowel lesions and high TGA levels at diagnosis (25–27). IgG based tests and radio immune assay (RIA) based TGA measurements are not suitable for monitoring response to a GFD in IgA sufficient patients with CD.…”

“…The search identified a total of 167 records, of which 17 were included: all primary observational studies (2128 children). We included one article published after March 2020 (26).…”

“…Although CD serology markers (IgA-TGA and endomysial autoantibodies (EmA)) work very well for diagnosis, these are less accurate for dietary monitoring (74,75). Dynamics of CD-antibodies after diagnosis may vary according to the adherence to the GFD, the timeframe of testing, type of antibodies, age at diagnosis, coexisting diseases (IgA deficiency, type 1 diabetes), antibody levels at diagnosis, and by assays used (25,26,(76)(77)(78)(79)(80)(81)(82)(83).…”

Quantification of Accidental Gluten Contamination in the Diet of Children with Treated Celiac Disease

“…Even more importantly, most of our patients (85%) with anti-tTG positivity were investigated during the first two years of GFD treatment. It is well established that normalization of IgA anti-tTG levels after starting the GFD may take longer than two years in a significant proportion of cases [19].…”