Gluten-related immunogenic peptides in stool as means to monitor compliance with gluten-free diet in children with newly diagnosed coeliac disease

Česká verzia

Authors: Vyhnánek R. ¹; Khaznadar Z. ²; Paulík M. ²
Authors place of work: Pediatrická klinika 1. LF UK a FTN, Praha ¹; Imunologická laboratoř, FTN, Praha ²
Published in the journal: Gastroent Hepatol 2021; 75(6): 519-523
Category: Paediatric gastroenterology and hepatology: original article
doi: https://doi.org/10.48095/ccgh2021519

Summary

Objectives and study: To compare the values of gluten-related immunogenic peptides (GIP) in stool and anti-tissue transglutaminase IgA antibodies (anti-tTG IgA) in blood in children newly diagnosed with coeliac disease (CD). Methods: All children (2–15 y) newly diagnosed with CD between May 2018 and May 2020 at our clinic who complied with the inclusion criteria were invited to join the prospective study. During workup for CD, a stool sample to measure GIP was taken together with a blood sample to measure anti-tTG IgA. All newly diagnosed children were invited 4 months later for a check-up. Children and their caregivers were asked about known non-compliance with the gluten-free diet (GFD), a blood sample was taken to measure the anti-tTG IgA, and a stool sample was collected to measure GIP. Blood was evaluated for anti-tTG IgA by ELISA, and the stool was tested by quantitative Sandwich ELISA designed to detect and quantify GIP using the G12 antibody. Values of GIP and anti-tTG IgA were compared in terms of their relation to the upper limit of normal (ULN) of the particular method. Results: 29 children (18 girls) were enrolled in the study. The values of GIP in stool at the time of diagnosis were above the ULN (0.15 µg/g) in all children. Average 4.21, median 3.29, standard deviation (SD) 3.7. After the four months, all but three (89.7%) had values of GIP in the reference range. Average 0.29, median 0.12, SD 0.73. Similarly, anti-tTG IgA values were above the ULN (9.9 U/mL) at the time of diagnosis in all children. Average 164, median 195, SD 49. Although the anti-tTG IgA levels were lower at check-up in all but one child, only 10 (34.5%) showed values within the normal range, with an average of 27.9, median 12.0, and SD 38.9. All children declared strict adherence to GFD. Discussion: Using the GIP concentration in stool, adherence to GFD in our cohort of children is very good, better than that described in literature. Conclusion: Measuring GIP in stool could prove a more sensitive indicator of adherence to GFD in the early months after the diagnosis of CD when anti-tTG IgA are still elevated above the ULN due to their well-described gradual decrease after GFD initiation.

Keywords:

compliance – Celiac disease – Gluten – immunogenic peptides

Zdroje

1. Kubina M, Čierna I, Székyová D et al. Niektoré genetické determinanty celiakie, význam HLA typizácie v klinickej praxi a zastúpenie HLA-DQ haplotypov v súbore 306 detských pacientov. Gastroent Hepatol 2016; 70 (6): 475–479. doi: 10.14735/amgh2016475.

2. Husby S, Koletzko S, Korponay-Szabó IR et al. European society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54 (1): 136–160. doi: 10.1097/MPG.0b013e31821a23d0.

3. Singh P, Arora A, Strand TA et al. Global prevalence of celiac disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018; 16 (6): 823–836.e2. doi: 10.1016/j.cgh.2017.06.037.

4. Husby S, Koletzko S, Korponay-Szabó I et al. European society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr 2020; 70 (1): 141–156. doi: 10.1097/MPG.0000000000002497.

5. Šibíková M, David J, Lhotská J et al. Závažný průběh celiakie, Čes-slov Pediat 2019; 74 (5): 275–279.

6. Czaja-Bulsa G, Bulsa M. Adherence to gluten-free diet in children with celiac disease. Nutrients 2018; 10 (10): 1424. doi: 10.3390/nu10101424.

7. Lebwohl B, Rubio-Tapia A. Epidemiology, presentation, and diagnosis of celiac disease. Gastroenterology 2021; 160 (1): 63–75. doi: 10.1053/j.gastro.2020.06.098.

8. Chvátalová T, Vepřeková G, Houska H et al. Celiac disease – a missed diagnosis. Vnitr Lek 2012; 58 (2): 99–103.

9. Sbravati F, Cosentino A, Lenzi J et al. Anti tissue transglutaminase antibodies‘ normalization after starting a gluten-free diet in a large population of celiac children-a real-life experience. Dig Liver Dis 2021; S1590-8658 (21) 00340-6. doi: 10.1016/j.dld.2021.06.026.

10. Comino I, Fernández-Bañares F, Esteve M 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 (10): 1456–1465. doi: 10.1038/ajg.2016.439.

11. Morón B, Bethune MT, Comino I et al. Toward the assessment of food toxicity for celiac patients: characterization of monoclonal antibodies to a main immunogenic gluten peptide. PLoS One 2008; 3 (5): e2294. doi: 10.1371/journal.pone.0002294.

12. Silvester JA, Weiten D, Graff LA et al. Living gluten-free: adherence, knowledge, lifestyle adaptations and feelings towards a gluten-free diet. J Hum Nutr Diet 2016; 29 (3): 374–382. doi: 10.1111/jhn.12316.

13. Comino I, Real A, Vivas S et al. Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces. Am J Clin Nutr 2012; 95 (3): 670–677. doi: 10.3945/ajcn.111.026708.

14. Moreno ML, Rodríguez-Herrera A, Sousa C et al. Biomarkers to monitor gluten-free diet compliance in celiac patients. Nutrients 2017; 9 (1): 46. doi: 10.3390/nu9010046.

15. Porcelli B, Ferretti F, Biviano I et al. Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs. Ann Gastroenterol 2020; 33 (6): 631–637. doi: 10.20524/aog.2020.0530.

16. Laserna-Mendieta EJ, Casanova MJ, Arias Á et al. Poor sensitivity of fecal gluten immunogenic peptides and serum antibodies to detect duodenal mucosal damage in celiac disease monitoring. Nutrients 2020; 13 (1): 98. doi: 10.3390/nu13010098.

17. Frühauf P, Bronský J, Dědek P et al. Celiakie – doporučený postup pro diagnostiku a terapii u dětí a dospívajících. Čes-slov Pediat 2016; 71 (3): 175–183.