Abstract
Objectives
Tissue transglutaminase (tTG) IgA antibodies are a hallmark for celiac disease (CD). In CD patients on gluten free diet (GFD) these antibodies are transient. Few studies are available comparing the tTG-IgA assay characteristics for monitoring response to GFD. Since discrepant results were reported in patients on GFD after switching tTG-IgA assays, we conducted a retrospective observational study to monitor GFD response using three different tTG-IgA assays.
Methods
Diagnostic samples from 44 adults and 17 children with CD were included. Of most patients two follow-up samples after introduction of GFD were available. In all samples tTG-IgA were assessed using one fluorochrome-enzyme immuno-assay (FEIA) and two chemiluminescence immuno-assays (CLIA) and intestinal fatty acid binding protein (i-FABP) as surrogate marker for intestinal epithelial damage was measured.
Results
Using CLIA assays, normalization of antibody levels was delayed compared to FEIA (p<0.001). Of all samples taken after at least 6 months on GFD with elevated i-FABP indicating intestinal epithelial damage, 40 % had positive tTG-IgA according to the FEIA, 85 and 90 % according to the two CLIA.
Conclusions
Normalization of tTG-IgA in patients on GFD depends on the assay used. Both CLIA appear to be more sensitive in detecting suboptimal treatment response in CD-indicated by elevated i-FABP – when applying the manufacturer’s recommended cut-off for the diagnosis of CD.
-
Research ethics: The study complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration.
-
Informed consent: Because of the anonymous nature of the data and the opt-out option described on our institutions’ homepages and request forms, the requirement for additional informed consent to participate in this study was deemed unnecessary according to the Dutch ‘‘Ethical Guidelines for Responsible Handling of Human Tissue for Scientific Research”.
-
Author contributions: Conceptualization: LM, JD and HB. Methodology: LM, JD, MV and HB Laboratory analysis: JH, TK, and CB. Data analysis: LM. Statistics: MV. Data Curation: LM, Writing – Original Draft Preparation: LM, Writing - Review and editing: JD, HB, DC and PvdP. The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: The authors report no conflict of interest relevant for the study presented. JD reports consultancy and/or speakers fees from Werfen/Inova, Thermo Fisher Scientific, and Euroimmun Medizinische Labordiagnostika.
-
Research funding: All tTG-IgA reagents were kindly provided by Thermo Fisher Scientific, Inova Diagnostics and Euroimmun Medizinische Labordiagnostika.
-
Data availability: The raw data can be obtained on request from the corresponding author.
References
1. Comino, I, Segura, V, Ortigosa, L, Espín, B, Castillejo, G, Garrote, JA, et al.. Prospective longitudinal study: use of faecal gluten immunogenic peptides to monitor children diagnosed with coeliac disease during transition to a gluten-free diet. Aliment Pharmacol Ther 2019;49:1484–92. https://doi.org/10.1111/apt.15277.Search in Google Scholar PubMed PubMed Central
2. Fang, H, King, KS, Larson, JJ, Snyder, MR, Wu, TT, Gandhi, MJ, et al.. Undetectable negative tissue transglutaminase IgA antibodies predict mucosal healing in treated coeliac disease patients. Aliment Pharmacol Ther 2017;46:681–7. https://doi.org/10.1111/apt.14250.Search in Google Scholar PubMed
3. Leonard, MM, Weir, DC, DeGroote, M, Mitchell, PD, Singh, P, Silvester, JA, et al.. Value of IgA tTG in predicting mucosal recovery in children with celiac disease on a gluten-free diet. J Pediatr Gastroenterol Nutr 2017;64:286–91. https://doi.org/10.1097/mpg.0000000000001460.Search in Google Scholar PubMed PubMed Central
4. Mulder, CJJ, Elli, L, Lebwohl, B, Makharia, GK, Rostami, K, Rubio-Tapia, A, et al.. Follow-up of celiac disease in adults: “when, what, who, and where”. Nutrients 2023;15:2048. https://doi.org/10.3390/nu15092048.Search in Google Scholar PubMed PubMed Central
5. Rubio-Tapia, A, Hill, ID, Semrad, C, Kelly, CP, Greer, KB, Limketkai, BN, et al.. American college of gastroenterology Guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol 2023;118:59–76. https://doi.org/10.14309/ajg.0000000000002075.Search in Google Scholar PubMed
6. Al-Toma, A, Volta, U, Auricchio, R, Castillejo, G, Sanders, DS, Cellier, C, et al.. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United Eur Gastroenterol J 2019;7:583–613. https://doi.org/10.1177/2050640619844125.Search in Google Scholar PubMed PubMed Central
7. Mahroum, N, Damoiseaux, J, Zoubi, M, Lavine, N, Ohayon, A, Amital, H, et al.. The mosaic of autoimmunity – a taste for more. The 12th international congress of autoimmunity 2021 (AUTO12) virtual. Autoimmun Rev 2021;20:102945. https://doi.org/10.1016/j.autrev.2021.102945.Search in Google Scholar PubMed
8. Sengul, OK, Akkelle, BS, Ay, P, Volkan, B, Tutar, E, Celikel, CA, et al.. Evaluation of mucosal status in the follow-up of pediatric patients with celiac disease: the role of serology. Eur J Pediatr 2022;181:3283–9. https://doi.org/10.1007/s00431-022-04535-3.Search in Google Scholar PubMed
9. Comino, I, Fernández-Bañares, F, Esteve, M, Ortigosa, L, Castillejo, G, Fambuena, B, et al.. Fecal gluten peptides reveal limitations of serological tests and food questionnaires for monitoring gluten-free diet in celiac disease patients. Am J Gastroenterol 2016;111:1456–65. https://doi.org/10.1038/ajg.2016.439.Search in Google Scholar PubMed PubMed Central
10. Bazzigaluppi, E, Roggero, P, Parma, B, Brambillasca, MF, Meroni, F, Mora, S, et al.. Antibodies to recombinant human tissue-transglutaminase in coeliac disease: diagnostic effectiveness and decline pattern after gluten-free diet. Dig Liver Dis 2006;38:98–102. https://doi.org/10.1016/j.dld.2005.10.020.Search in Google Scholar PubMed
11. Spatola, BN, Kaukinen, K, Collin, P, Mäki, M, Kagnoff, MF, Daugherty, P. Persistence of elevated deamidated gliadin peptide antibodies on a gluten-free diet indicates nonresponsive coeliac disease. Aliment Pharmacol Therapeut 2014;39:407–17. https://doi.org/10.1111/apt.12603.Search in Google Scholar PubMed PubMed Central
12. Adriaanse, MP, Leffler, DA, Kelly, CP, Schuppan, D, Najarian, RM, Goldsmith, JD, et al.. Serum I-FABP detects gluten responsiveness in adult Celiac Disease patients on a short-term gluten challenge. Aliment Pharmacol Ther 2016;111:1014–22. https://doi.org/10.1038/ajg.2016.162.Search in Google Scholar PubMed
13. Rodríguez-Martín, L, Vaquero, L, Vivas, S. Letter: serum I-FABP as marker for enterocyte damage in first-degree relatives of patients with coeliac disease. Aliment Pharmacol Ther 2015;42:121–2. https://doi.org/10.1111/apt.13187.Search in Google Scholar PubMed
14. Adriaanse, MP, Buurman, WA, Vreugdenhil, AC. Letter: serum I-FABP as marker for enterocyte damage in first-degree relatives of patients with coeliac disease – authors’ reply. Aliment Pharmacol Ther 2015;42:122. https://doi.org/10.1111/apt.13240.Search in Google Scholar PubMed
15. Logan, M, MacKinder, M, Clark, CM, Kountouri, A, Jere, M, Ijaz, UZ, et al.. Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn’s disease. BMC Gastroenterol 2022;22:260. https://doi.org/10.1186/s12876-022-02334-6.Search in Google Scholar PubMed PubMed Central
16. Gross, S, Adriaanse, MP, Nijeboer, P, Tack, GJ, van Hoogstraten, IM, Bouma, G, et al.. Serum intestinal-fatty acid binding protein as a biomarker for refractory celiac disease. J Gastrointestin Liver Dis 2015;24:258–9.Search in Google Scholar
17. Silvester, JA, Kurada, S, Szwajcer, A, Kelly, CP, Leffler, DA, Duerksen, DR. 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. Gastroenterology 2017;153:689–701. https://doi.org/10.1053/j.gastro.2017.05.015.Search in Google Scholar PubMed PubMed Central
18. Castelijn, DAR, Mulder, AHL, Pol van der, P, Hollander, JC, Kuiper, T, Bijnens, C, et al.. Retrospective multicenter study to compare the diagnostic performance of CLIA versus FEIA tissue transglutaminase IgA tests for the diagnosis of celiac disease. Clin Chem Lab Med 2023;61:1446–54. https://doi.org/10.1515/cclm-2022-1045.Search in Google Scholar PubMed
19. Sansotta, N, Alessio, MG, Norsa, L, Previtali, G, Ferrari, A, Guerra, G, et al.. Trend of antitissue transglutaminase antibody normalization in children with celiac disease started on gluten-free diet: a comparative study between chemilumininescence and ELISA serum assays. J Pediatr Gastroenterol Nutr 2020;70:37–41. https://doi.org/10.1097/mpg.0000000000002519.Search in Google Scholar
20. Nevejan, L, Dobbels, P, Norman, GL, Voreck, A, Bossuyt, X, Van Hoovels, L. Necessity of harmonization of tissue transglutaminase IgA assays to align clinical decision making in coeliac disease. Clin Chem Lab Med 2022;60:81–4. https://doi.org/10.1515/cclm-2021-1207.Search in Google Scholar PubMed
21. Vreugdenhil, AC, Wolters, VM, Adriaanse, MP, Van den Neucker, AM, van Bijnen, AA, Houwen, R, et al.. Additional value of serum I-FABP levels for evaluating celiac disease activity in children. Scand J Gastroenterol 2011;46:1435–41. https://doi.org/10.3109/00365521.2011.627447.Search in Google Scholar PubMed
22. Blaser, A, Padar, M, Tang, J, Dutton, J, Forbes, A. Citrulline and intestinal fatty acid-binding protein as biomarkers for gastrointestinal dysfunction in the critically ill. Anaesthesiol Intensive Ther 2019;51:230–9. https://doi.org/10.5114/ait.2019.86049.Search in Google Scholar PubMed
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2023-1076).
© 2023 Walter de Gruyter GmbH, Berlin/Boston