Home Monitoring patients with celiac disease on gluten free diet: different outcomes comparing three tissue transglutaminase IgA assays
Article
Licensed
Unlicensed Requires Authentication

Monitoring patients with celiac disease on gluten free diet: different outcomes comparing three tissue transglutaminase IgA assays

  • A.H. Leontine Mulder ORCID logo EMAIL logo , Daan A.R. Castelijn ORCID logo , Pieter van der Pol , Marloes Vermeer , Jolien C. Hollander , Tietie Kuiper , Caroline Bijnens , Hetty J. Bontkes and Jan Damoiseaux ORCID logo
Published/Copyright: November 10, 2023
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 4

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.

Keywords: celiac disease; tissue transglutaminase (tTG)-IgA; monitoring gluten free diet response; intestinal fatty acid binding protein (i-FABP)
Corresponding author: A.H. Leontine Mulder, Clinical Laboratory, Unilabs, P.O. Box 50 000, 7500 KA, Enschede, The Netherlands; and Department of Clinical Chemistry, Ziekenhuis Groep Twente, Almelo, The Netherlands, E-mail:

  1. Research ethics: The study complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration.

  2. 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”.

  3. 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.

  4. 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.

  5. Research funding: All tTG-IgA reagents were kindly provided by Thermo Fisher Scientific, Inova Diagnostics and Euroimmun Medizinische Labordiagnostika.

  6. 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).

Received: 2023-07-20
Accepted: 2023-10-24
Published Online: 2023-11-10
Published in Print: 2024-03-25

© 2023 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Value-based laboratory medicine: the time is now
  4. Review
  5. Cardiovascular risk evaluation in pregnancy: focus on cardiac specific biomarkers
  6. Opinion Papers
  7. From volume to value: a watershed moment for the clinical laboratory
  8. APS calculator: a data-driven tool for setting outcome-based analytical performance specifications for measurement uncertainty using specific clinical requirements and population data
  9. Guidelines and Recommendations
  10. Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee
  11. Genetics and Molecular Diagnostics
  12. Specifications of qPCR based epigenetic immune cell quantification
  13. General Clinical Chemistry and Laboratory Medicine
  14. An appraisal of the practice of duplicate testing for the detection of irregular analytical errors
  15. Machine learning-based nonlinear regression-adjusted real-time quality control modeling: a multi-center study
  16. The effect of ratios upon improving patient-based real-time quality control (PBRTQC) performance
  17. Diagnostic sample transport via pneumatic tube systems: data logger and their algorithms are sensitive to transport effects
  18. Ambulatory human chorionic gonadotrophin (hCG) testing: a verification of two hCG point of care devices
  19. Monitoring patients with celiac disease on gluten free diet: different outcomes comparing three tissue transglutaminase IgA assays
  20. Verification, implementation and harmonization of automated chemiluminescent immunoassays for MPO- and PR3-ANCA detection
  21. Performance evaluation of a novel platelet count parameter, hybrid platelet count, on the BC-780 automated hematology analyzer
  22. Reference Values and Biological Variations
  23. Pediatric reference intervals for serum neurofilament light and glial fibrillary acidic protein using the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort
  24. Biological variation of serum neopterin concentrations in apparently healthy individuals
  25. Short-term biological variation of serum tryptase
  26. Cancer Diagnostics
  27. Quantification of the lung cancer tumor marker CYFRA 21-1 using protein precipitation, immunoaffinity bottom-up LC-MS/MS
  28. Cardiovascular Diseases
  29. Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome
  30. Deep learning-based NT-proBNP prediction from the ECG for risk assessment in the community
  31. Diabetes
  32. Innovations in HbA1c analysis: finding the balance between speed and accuracy. An investigation of a potential new Secondary Reference Measurement Procedure for the IFCC
  33. Precise glucose measurement in sodium fluoride-citrate plasma affects estimates of prevalence in diabetes and prediabetes
  34. Infectious Diseases
  35. Urinary phenotyping of SARS-CoV-2 infection connects clinical diagnostics with metabolomics and uncovers impaired NAD+ pathway and SIRT1 activation
  36. Letters to the Editor
  37. Analytical performance specifications for measurement uncertainty in therapeutic monitoring of immunosuppressive drugs
  38. Capillary blood collection tubes containing serum separator gel result in lower measurements of oestradiol and total testosterone
  39. Re.: Louise Guillaume et al. Biological variation of CA 15-3, CA 125 and HE 4 on lithium heparinate plasma in apparently healthy Caucasian volunteers. Clin Chem Lab Med 2023;61(7):1319–1326; https://doi.org/10.1515/cclm-2022-0966
  40. A comparison of cannabidiol (CBD) concentrations in venous vs. fingertip-capillary blood
  41. Identification of sulfamethoxazole’s residues in sulfamethoxazole induced kidney stones by mass spectrometry
  42. Impact of different preservation methods on urinary red blood cell counts
  43. Diagnosis of IRAK-4-deficiency by flow cytometric measurement of IκB-α degradation
https://doi.org/10.1515/cclm-2023-1076
Keywords for this article
celiac disease; tissue transglutaminase (tTG)-IgA; monitoring gluten free diet response; intestinal fatty acid binding protein (i-FABP)

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Value-based laboratory medicine: the time is now
  4. Review
  5. Cardiovascular risk evaluation in pregnancy: focus on cardiac specific biomarkers
  6. Opinion Papers
  7. From volume to value: a watershed moment for the clinical laboratory
  8. APS calculator: a data-driven tool for setting outcome-based analytical performance specifications for measurement uncertainty using specific clinical requirements and population data
  9. Guidelines and Recommendations
  10. Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee
  11. Genetics and Molecular Diagnostics
  12. Specifications of qPCR based epigenetic immune cell quantification
  13. General Clinical Chemistry and Laboratory Medicine
  14. An appraisal of the practice of duplicate testing for the detection of irregular analytical errors
  15. Machine learning-based nonlinear regression-adjusted real-time quality control modeling: a multi-center study
  16. The effect of ratios upon improving patient-based real-time quality control (PBRTQC) performance
  17. Diagnostic sample transport via pneumatic tube systems: data logger and their algorithms are sensitive to transport effects
  18. Ambulatory human chorionic gonadotrophin (hCG) testing: a verification of two hCG point of care devices
  19. Monitoring patients with celiac disease on gluten free diet: different outcomes comparing three tissue transglutaminase IgA assays
  20. Verification, implementation and harmonization of automated chemiluminescent immunoassays for MPO- and PR3-ANCA detection
  21. Performance evaluation of a novel platelet count parameter, hybrid platelet count, on the BC-780 automated hematology analyzer
  22. Reference Values and Biological Variations
  23. Pediatric reference intervals for serum neurofilament light and glial fibrillary acidic protein using the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort
  24. Biological variation of serum neopterin concentrations in apparently healthy individuals
  25. Short-term biological variation of serum tryptase
  26. Cancer Diagnostics
  27. Quantification of the lung cancer tumor marker CYFRA 21-1 using protein precipitation, immunoaffinity bottom-up LC-MS/MS
  28. Cardiovascular Diseases
  29. Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome
  30. Deep learning-based NT-proBNP prediction from the ECG for risk assessment in the community
  31. Diabetes
  32. Innovations in HbA1c analysis: finding the balance between speed and accuracy. An investigation of a potential new Secondary Reference Measurement Procedure for the IFCC
  33. Precise glucose measurement in sodium fluoride-citrate plasma affects estimates of prevalence in diabetes and prediabetes
  34. Infectious Diseases
  35. Urinary phenotyping of SARS-CoV-2 infection connects clinical diagnostics with metabolomics and uncovers impaired NAD+ pathway and SIRT1 activation
  36. Letters to the Editor
  37. Analytical performance specifications for measurement uncertainty in therapeutic monitoring of immunosuppressive drugs
  38. Capillary blood collection tubes containing serum separator gel result in lower measurements of oestradiol and total testosterone
  39. Re.: Louise Guillaume et al. Biological variation of CA 15-3, CA 125 and HE 4 on lithium heparinate plasma in apparently healthy Caucasian volunteers. Clin Chem Lab Med 2023;61(7):1319–1326; https://doi.org/10.1515/cclm-2022-0966
  40. A comparison of cannabidiol (CBD) concentrations in venous vs. fingertip-capillary blood
  41. Identification of sulfamethoxazole’s residues in sulfamethoxazole induced kidney stones by mass spectrometry
  42. Impact of different preservation methods on urinary red blood cell counts
  43. Diagnosis of IRAK-4-deficiency by flow cytometric measurement of IκB-α degradation
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 6.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2023-1076/html
Scroll to top button