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A Comparison of Antibody Testing, Permeability Testing, and Zonulin Levels with Small-Bowel Biopsy in Celiac Disease Patients on a Gluten-Free Diet

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Abstract

Active celiac disease is associated with positive endomysial (EMA) and tissue transglutaminase (TTG) antibodies, elevated zonulin levels, and increased intestinal permeability. There is little known about what happens to these immunologic and structural abnormalities in patients on a gluten-free diet and their correlation with small-bowel biopsy changes. Adult patients previously diagnosed with celiac disease and on a gluten-free diet for greater than 1 year were considered for the study. All patients underwent the following: measurement of EMA and TTG antibodies, serum zonulin levels, intestinal permeability (IP) testing with lactulose/mannitol ratios, food diary analysis for gluten ingestion and small- bowel biopsy. A total of 21 patients on a gluten-free diet for a mean of 9.7 years completed the study. There were ten patients who had normalization of intestinal biopsies, IP and TTG, and EM antibodies. Six patients had Marsh type 2 or 3 lesions and all had either abnormal IP (5/6) or TTG antibody (4/6). In patients with Marsh type 3 lesions, there was a correlation between IP and zonulin levels. A subgroup of patients with celiac disease on a gluten-free diet has complete normalization of intestinal biopsies, intestinal permeability defects, and antibody levels. Patients with Marsh type 3 lesions have abnormal TTG antibodies and intestinal permeability with zonulin levels that correlate with IP. These abnormalities may be due to continued gluten ingestion. Further study is needed to determine the clinical utility of TTG antibodies and IP testing in following patients with celiac disease.

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References

  1. Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357:1731–1743. doi:10.1056/NEJMra071600.

    Article  CAS  PubMed  Google Scholar 

  2. Sollid LM, Khosla C. Future therapeutic options for celiac disease. Nat Clin Pract Gastroenterol Hepatol. 2005;2:140–147. doi:10.1038/ncpgasthep0111.

    Article  CAS  PubMed  Google Scholar 

  3. Fasano A, Not T, Wang W, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000;355:1518–1519. doi:10.1016/S0140-6736(00)02169-3. (Letter).

    Article  CAS  PubMed  Google Scholar 

  4. Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut. 2006;55:1512–1520. doi:10.1136/gut.2005.085373.

    Article  CAS  PubMed  Google Scholar 

  5. Smecuol E, Bai JC, Vazquez H, et al. Gastrointestinal permeability in celiac disease. Gastroenterology. 1997;112:1129–1136. doi:10.1016/S0016-5085(97)70123-9.

    Article  CAS  PubMed  Google Scholar 

  6. Duerksen DR, Wilhelm-Boyles C, Parry DM. Intestinal permeability in long-term follow-up of patients with celiac disease on a gluten-free diet. Dig Dis Sci. 2005;50:785–790. doi:10.1007/s10620-005-2574-0.

    Article  CAS  PubMed  Google Scholar 

  7. Vahedi K, Mascart F, Mary JY, et al. Reliability of antitransglutaminase antibodies as predictors of gluten-free diet compliance in adult celiac disease. Am J Gastroenterol. 2003;98:1079–1087. doi:10.1111/j.1572-0241.2003.07284.x.

    Article  CAS  PubMed  Google Scholar 

  8. Uil JJ, van Elburg RR, Janssens PMW, Mulder CJJ, Heymans HSA. Sensitivity of a hyperosmolar or low-osmolar test solution for sugar absorption in recognizing small intestinal mucosal damage in coeliac disease. Dig Liver Dis. 2000;32:195–200. doi:10.1016/S1590-8658(00)80820-8.

    Article  CAS  PubMed  Google Scholar 

  9. Mariani P, Viti MG, Montuori M, et al. The gluten-free diet: a nutritional risk factor for adolescents with celiac disease? J Pediatr Gastroenterol Nutr. 1998;27:519–523. doi:10.1097/00005176-199811000-00004.

    Article  CAS  PubMed  Google Scholar 

  10. El Asmar R, Panigrahi P, Bamford P, et al. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology. 2002;123:1607–1615. doi:10.1053/gast.2002.36578.

    Article  CAS  PubMed  Google Scholar 

  11. Ravelli A, Bolognini S, Gambarotti M, Villanacci V. Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy. Am J Gastroenterol. 2005;100:177–185. doi:10.1111/j.1572-0241.2005.40669.x.

    Article  PubMed  Google Scholar 

  12. Drago S, El Asmar R, Di Pierro M, et al. Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006;41:408–419. doi:10.1080/00365520500235334.

    Article  CAS  PubMed  Google Scholar 

  13. Leffler DA, Edwards George JB, Dennis M, Cook EF, Schuppan D, Kelly CP. A prospective comparative study of five measures of gluten-free diet adherence in adults with coeliac disease. Aliment Pharmacol Ther. 2007;26:1227–1235.

    Article  CAS  PubMed  Google Scholar 

  14. Ciacci C, Cirillo M, Cavallaro R, Mazzacca G. Long-term follow-up of celiac adults on gluten-free diet: prevalence and correlates of intestinal damage. Digestion. 2002;66:178–185. doi:10.1159/000066757.

    Article  CAS  PubMed  Google Scholar 

  15. Fabiani E, Taccari LM, Ratsch IM, Di-Giuseppe S, Coppa GV, Catassi C. Compliance with gluten-free diet in adolescents with screening-detected celiac disease: a 5-year follow-up study. J Pediatr. 2000;136:841–843.

    Article  CAS  PubMed  Google Scholar 

  16. Bardella MT, Molteni N, Prampolini L, et al. Need for follow up in coeliac disease. Arch Dis Child. 1994;70:211–213. doi:10.1136/adc.70.3.211.

    Article  CAS  PubMed  Google Scholar 

  17. Faulkner-Hogg KB, Selby WS, Loblay RH. Dietary analysis in symptomatic patients with coeliac disease on a gluten-free diet: the role of trace amounts of gluten and non-gluten food intolerances. Scand J Gastroenterol. 1999;34:784–789. doi:10.1080/003655299750025714.

    Article  CAS  PubMed  Google Scholar 

  18. Pietzak MM. Follow-up of patients with celiac disease: achieving compliance with treatment. Gastroenterology. 2005;128:S135–S141. doi:10.1053/j.gastro.2005.02.025.

    Article  PubMed  Google Scholar 

  19. Brandimarte G, Tursi A, Giorgetti GM. Changing trends in clinical form of celiac disease. Which is now the main form of celiac disease in clinical practice? Minerva Gastroenterol Dietol. 2002;48:121–130.

    CAS  PubMed  Google Scholar 

  20. Rubio-Tapia A, Kelly DG, Lahr BD, Dogan A, Wu TT, Murray JA. Clinical staging and survival in refractory celiac disease: a single center experience. Gastroenterology. 2009;136:99–107. doi:10.1053/j.gastro.2008.10.013.

    Article  PubMed  Google Scholar 

  21. Sapone A, de Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55:1443–1449. doi:10.2337/db05-1593.

    Article  CAS  PubMed  Google Scholar 

  22. Lee SK, Lo W, Memeo L, Rotterdam H, Green PH. Duodenal histology in patients with celiac disease after treatment with a gluten-free diet. Gastrointest Endosc. 2003;57:187–191. doi:10.1067/mge.2003.54.

    Article  PubMed  Google Scholar 

  23. Ciclitira PJ, Johnson MW, Dewar DH, Ellis HJ. The pathogenesis of coeliac disease. Mol Aspects Med. 2005;26:421–458. doi:10.1016/j.mam.2005.05.001.

    Article  CAS  PubMed  Google Scholar 

  24. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1–19. doi:10.1097/00005176-200501000-00001.

    Article  PubMed  Google Scholar 

  25. Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006;131:1981–2002. doi:10.1053/j.gastro.2006.10.004.

    Article  PubMed  Google Scholar 

  26. Dickey W, Hughes DF, McMillan SA. Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery. Am J Gastroenterol. 2000;95:712–714. doi:10.1111/j.1572-0241.2000.01838.x.

    Article  CAS  PubMed  Google Scholar 

  27. Vilela EG, Abreu Ferrari ML, Gama Torres HO, et al. Intestinal permeability and antigliadin antibody test for monitoring adult patients with celiac disease. Dig Dis Sci. 2007;52:1304–1309. doi:10.1007/s10620-006-9511-8.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. A. Fasano (University of Maryland) for his review of the small-bowel biopsies and his helpful review of this manuscript. This study was supported by a grant from the Manitoba Medical Services Foundation.

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Correspondence to D. R. Duerksen.

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Duerksen, D.R., Wilhelm-Boyles, C., Veitch, R. et al. A Comparison of Antibody Testing, Permeability Testing, and Zonulin Levels with Small-Bowel Biopsy in Celiac Disease Patients on a Gluten-Free Diet. Dig Dis Sci 55, 1026–1031 (2010). https://doi.org/10.1007/s10620-009-0813-5

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  • DOI: https://doi.org/10.1007/s10620-009-0813-5

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