Abstract
We previously developed an in vitro organ culture system in which gluten exerts a toxic effect on intestinal mucosa of patients with active gluten-sensitive enteropathy. Gluten generally inhibits the epithelial cell maturation of intestinal biopsy specimens that otherwise occurs if the tissue is cultured for 24-48 h in a gluten-free medium. However, small intestinal mucosa from 15-20% of patients with proven gluten-sensitive enteropathy fails to manifest the expected gluten-induced damage in vitro. In the present study, we explored the relation between in vitro gluten-induced intestinal damage and the presence of HLA-B8. We determined whether the patients' histocompatibility type (HLA-B8 positive or negative) influenced the ability of gluten protein to inhibit epithelial cell maturation of cultured intestinal biopsy specimens from patients with gluten-sensitive enteropathy.
Intestinal biopsies from 21 of 24 patients with gluten-sensitive enteropathy and HLA-B8 showed gluten-induced damage in vitro. On the other hand, intestinal biopsies from only 4 of 16 patients with gluten-sensitive enteropathy but without HLA-B8 showed gluten-induced damage in vitro. The difference in the effect of gluten in vitro between these two groups was statistically significant (P < 0.01). The data show a dichotomy between gluten-induced tissue damage in vivo and in vitro in HLA-B8 negative patients, suggesting that HLA-B8 is important for gluten to manifest a cytotoxic influence in organ culture.
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- BRANDBORG L. L., RUBIN G. E., QUINTON W. E. A multipurpose instrument for suction biopsy of the esophagus, stomach, small bowel, and colon. Gastroenterology. 1959 Jul;37(1):1–16. [PubMed] [Google Scholar]
- Douglas A. P. The binding of a glycopeptide component of wheat gluten to intestinal mucosa of normal and coeliac human subjects. Clin Chim Acta. 1976 Dec 1;73(2):357–361. doi: 10.1016/0009-8981(76)90183-2. [DOI] [PubMed] [Google Scholar]
- FRAZER A. C., FLETCHER R. F., ROSS C. A., SHAW B., SAMMONS H. G., SCHNEIDER R. Gluten-induced enteropathy: the effect of partially digested gluten. Lancet. 1959 Sep 5;2(7097):252–255. doi: 10.1016/s0140-6736(59)92051-3. [DOI] [PubMed] [Google Scholar]
- Falchuk Z. M., Gebhard R. L., Sessoms C., Strober W. An in vitro model of gluten-sensitive enteropathy. Effect of gliadin on intestinal epithelial cells of patients with gluten-sensitive enteropathy in organ culture. J Clin Invest. 1974 Feb;53(2):487–500. doi: 10.1172/JCI107582. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Falchuk Z. M., Rogentine G. N., Strober W. Predominance of histocompatibility antigen HL-A8 in patients with gluten-sensitive enteropathy. J Clin Invest. 1972 Jun;51(6):1602–1605. doi: 10.1172/JCI106958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Falchuk Z. M., Strober W. Gluten-sensitive enteropathy: synthesis of antigliadin antibody in vitro. Gut. 1974 Dec;15(12):947–952. doi: 10.1136/gut.15.12.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferguson A., MacDonald T. T., McClure J. P., Holden R. J. Cell-mediated immunity to gliadin within the small-intestinal mucosa in coeliac disease. Lancet. 1975 Apr 19;1(7912):895–897. doi: 10.1016/s0140-6736(75)91689-x. [DOI] [PubMed] [Google Scholar]
- Katz A. J., Falchuk Z. M. Definitive diagnosis of gluten-sensitive enteropathy. Use of an in vitro organ culture model. Gastroenterology. 1978 Oct;75(4):695–700. [PubMed] [Google Scholar]
- Keuning J. J., Peña A. S., van Leeuwen A., van Hooff J. P., va Rood J. J. HLA-DW3 associated with coeliac disease. Lancet. 1976 Mar 6;1(7958):506–508. doi: 10.1016/s0140-6736(76)90294-4. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Mann D. L., Katz S. I., Nelson D. L., Abelson L. D. Specific B-cell antigens associated with gluten-sensitive enteropathy and dermatitis herpetiformis. Lancet. 1976 Jan 17;1(7951):110–111. doi: 10.1016/s0140-6736(76)93153-6. [DOI] [PubMed] [Google Scholar]
- Mittal K. K., Mickey M. R., Singal D. P., Terasaki P. I. Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation. 1968 Nov;6(8):913–927. doi: 10.1097/00007890-196811000-00006. [DOI] [PubMed] [Google Scholar]
- RUBIN W., FAUCI A. S., MARVIN S. F., SLEISENGER M. H., JEFRIES G. H. IMMUNOFLUORESCENT STUDIES IN ADULT CELIAC DISEASE. J Clin Invest. 1965 Mar;44:475–485. doi: 10.1172/JCI105161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shearer G. M., Schmitt-Verhulst A. M. Major histocompatibility complex restricted cell-mediated immunity. Adv Immunol. 1977;25:55–91. doi: 10.1016/s0065-2776(08)60931-1. [DOI] [PubMed] [Google Scholar]
- Stokes P. L., Asquith P., Holmes G. K., Mackintosh P., Cooke W. T. Histocompatibility antigens associated with adult coeliac disease. Lancet. 1972 Jul 22;2(7769):162–164. doi: 10.1016/s0140-6736(72)91330-x. [DOI] [PubMed] [Google Scholar]
- Weiser M. M., Douglas A. P. An alternative mechanism for gluten toxicity in coeliac disease. Lancet. 1976 Mar 13;1(7959):567–569. doi: 10.1016/s0140-6736(76)90361-5. [DOI] [PubMed] [Google Scholar]