Skip to main content
PMC home page
Gut logoLink to Gut
. 1993 Nov;34(11):1515–1519. doi: 10.1136/gut.34.11.1515

Dose dependent effects of protracted ingestion of small amounts of gliadin in coeliac disease children: a clinical and jejunal morphometric study.

C Catassi 1, M Rossini 1, I M Rätsch 1, I Bearzi 1, A Santinelli 1, R Castagnani 1, E Pisani 1, G V Coppa 1, P L Giorgi 1
PMCID: PMC1374413  PMID: 8244135

Abstract

This study aimed to investigate the effects of chronic ingestion of small amounts of gliadin on children with coeliac disease. A four week challenge was performed on 20 children who had been on a gluten free diet for mean (SD) 14 (3) months. They were given a daily dose of either 100 mg (group A, n = 10, mean age 4 (2) years) or 500 mg of gliadin (group B, mean age 5 (3) years). The effects of the gliadin were monitored by morphometric study of the jejunal mucosa, intestinal permeability test with cellobiose/mannitol, and serum antigliadin antibody test. After the challenge, group A patients showed a significant increase in the mean intraepithelial lymphocyte count (before challenge 11 (3), afterwards 19 (6)) and a decrease in the villous height/crypt depth ratio (beforehand 1.5 (0.1), afterwards 1.3 (0.2)), while the intestinal permeability test remained normal and the IgA-antigliadin antibody increased in four of 10 children. After the challenge group B showed more pronounced histological changes, an increase in the mean urinary cellobiose/mannitol % (beforehand 0.028 (0.020), afterwards 0.058 (0.028)), and IgA-antigliadin antibody positivity in six of eight subjects. The discriminant analysis function showed that the pretreatment group, group A after challenge, and group B after challenge were correctly classified in 90% of cases by functions based on the individual intraepithelial lymphocyte count and the villous height/crypt depth ratio. This study shows that chronic ingestion of small amounts of gluten causes dose-dependent damage to the small intestinal mucosa in children with coeliac disease. The predictive value of laboratory tests, such as the antigliadin antibody test and the intestinal permeability test seems to be lower in treated patients than in those with active coeliac disease.

Full text

PDF
1515

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bjarnason I., Peters T. J., Veall N. A persistent defect in intestinal permeability in coeliac disease demonstrated by a 51Cr-labelled EDTA absorption test. Lancet. 1983 Feb 12;1(8320):323–325. doi: 10.1016/s0140-6736(83)91628-8. [DOI] [PubMed] [Google Scholar]
  2. Brandtzaeg P., Halstensen T. S., Kett K., Krajci P., Kvale D., Rognum T. O., Scott H., Sollid L. M. Immunobiology and immunopathology of human gut mucosa: humoral immunity and intraepithelial lymphocytes. Gastroenterology. 1989 Dec;97(6):1562–1584. doi: 10.1016/0016-5085(89)90406-x. [DOI] [PubMed] [Google Scholar]
  3. Catassi C., Pierani P., Natalini G., Gabrielli O., Coppa G. V., Giorgi P. L. Clinical application of a simple HPLC method for the sugar intestinal permeability test. J Pediatr Gastroenterol Nutr. 1991 Feb;12(2):209–212. doi: 10.1097/00005176-199102000-00012. [DOI] [PubMed] [Google Scholar]
  4. Ciclitira P. J., Cerio R., Ellis H. J., Maxton D., Nelufer J. M., Macartney J. M. Evaluation of a gliadin-containing gluten-free product in coeliac patients. Hum Nutr Clin Nutr. 1985 Jul;39(4):303–308. [PubMed] [Google Scholar]
  5. Ciclitira P. J., Ellis H. J., Fagg N. L. Evaluation of a gluten free product containing wheat gliadin in patients with coeliac disease. Br Med J (Clin Res Ed) 1984 Jul 14;289(6437):83–83. doi: 10.1136/bmj.289.6437.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ciclitira P. J., Evans D. J., Fagg N. L., Lennox E. S., Dowling R. H. Clinical testing of gliadin fractions in coeliac patients. Clin Sci (Lond) 1984 Mar;66(3):357–364. doi: 10.1042/cs0660357. [DOI] [PubMed] [Google Scholar]
  7. Congdon P., Mason M. K., Smith S., Crollick A., Steel A., Littlewood J. Small-bowel mucosa in asymptomatic children with celiac disease. Mucosal changes with gluten-free diets. Am J Dis Child. 1981 Feb;135(2):118–121. doi: 10.1001/archpedi.1981.02130260010004. [DOI] [PubMed] [Google Scholar]
  8. Ferguson A., Murray D. Quantitation of intraepithelial lymphocytes in human jejunum. Gut. 1971 Dec;12(12):988–994. doi: 10.1136/gut.12.12.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freedman A. R., Macartney J. C., Nelufer J. M., Ciclitira P. J. Timing of infiltration of T lymphocytes induced by gluten into the small intestine in coeliac disease. J Clin Pathol. 1987 Jul;40(7):741–745. doi: 10.1136/jcp.40.7.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hall E. J., Batt R. M. Abnormal permeability precedes the development of a gluten sensitive enteropathy in Irish setter dogs. Gut. 1991 Jul;32(7):749–753. doi: 10.1136/gut.32.7.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hamilton J. R., McNeill L. K. Childhood celiac disease: response of treated patients to a small uniform daily dose of wheat gluten. J Pediatr. 1972 Nov;81(5):885–893. doi: 10.1016/s0022-3476(72)80538-9. [DOI] [PubMed] [Google Scholar]
  12. Hekkens W. T. The determination of prolamins in gluten-free food. Introductory remarks. Panminerva Med. 1991 Apr-Jun;33(2):61–64. [PubMed] [Google Scholar]
  13. Juby L. D., Dixon M. F., Axon A. T. Abnormal intestinal permeability and jejunal morphometry. J Clin Pathol. 1987 Jul;40(7):714–718. doi: 10.1136/jcp.40.7.714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lavö B., Knutson L., Löf L., Hällgren R. Gliadin challenge-induced jejunal prostaglandin E2 secretion in celiac disease. Gastroenterology. 1990 Sep;99(3):703–707. doi: 10.1016/0016-5085(90)90958-4. [DOI] [PubMed] [Google Scholar]
  15. Lavö B., Knutson L., Löf L., Odlind B., Hällgren R. Signs of increased leakage over the jejunal mucosa during gliadin challenge of patients with coeliac disease. Gut. 1990 Feb;31(2):153–157. doi: 10.1136/gut.31.2.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leigh R. J., Marsh M. N., Crowe P., Kelly C., Garner V., Gordon D. Studies of intestinal lymphoid tissue. IX. Dose-dependent, gluten-induced lymphoid infiltration of coeliac jejunal epithelium. Scand J Gastroenterol. 1985 Aug;20(6):715–719. doi: 10.3109/00365528509089201. [DOI] [PubMed] [Google Scholar]
  17. Marsh M. N. Grains of truth: evolutionary changes in small intestinal mucosa in response to environmental antigen challenge. Gut. 1990 Jan;31(1):111–114. doi: 10.1136/gut.31.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Montgomery A. M., Goka A. K., Kumar P. J., Farthing M. J., Clark M. L. Low gluten diet in the treatment of adult coeliac disease: effect on jejunal morphology and serum anti-gluten antibodies. Gut. 1988 Nov;29(11):1564–1568. doi: 10.1136/gut.29.11.1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nathavitharana K. A., Lloyd D. R., Raafat F., Brown G. A., McNeish A. S. Urinary mannitol: lactulose excretion ratios and jejunal mucosal structure. Arch Dis Child. 1988 Sep;63(9):1054–1059. doi: 10.1136/adc.63.9.1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Packer S. M., Charlton V., Keeling J. W., Risdon R. A., Ogilvie D., Rowlatt R. J., Larcher V. F., Harries J. T. Gluten challenge in treated coeliac disease. Arch Dis Child. 1978 Jun;53(6):449–455. doi: 10.1136/adc.53.6.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Penna F. J., Hill I. D., Kingston D., Robertson K., Slavin G., Shiner M. Jejunal mucosal morphometry in children with and without gut symptoms and in normal adults. J Clin Pathol. 1981 Apr;34(4):386–392. doi: 10.1136/jcp.34.4.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Savilahti E., Viander M., Perkkiö M., Vainio E., Kalimo K., Reunala T. IgA antigliadin antibodies: a marker of mucosal damage in childhood coeliac disease. Lancet. 1983 Feb 12;1(8320):320–322. doi: 10.1016/s0140-6736(83)91627-6. [DOI] [PubMed] [Google Scholar]
  23. Schaad U. B., Gaze H., Hadorn B. Intraepithelial lymphocytes before and after gluten challenge in children with celiac disease. Am J Dis Child. 1981 Mar;135(3):272–273. doi: 10.1001/archpedi.1981.02130270064022. [DOI] [PubMed] [Google Scholar]
  24. Scotta M. S., De Giacomo C., Maggiore G., Siena S., Ugazio A. G. Eucharistic problems for celiac patients. N Engl J Med. 1982 Sep 30;307(14):898–898. doi: 10.1056/nejm198209303071423. [DOI] [PubMed] [Google Scholar]
  25. Troncone R., Ferguson A. Anti-gliadin antibodies. J Pediatr Gastroenterol Nutr. 1991 Feb;12(2):150–158. doi: 10.1097/00005176-199102000-00002. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES