Increased small intestinal apoptosis in coeliac disease.
Open Access
- 1 December 1996
- Vol. 39 (6), 811-817
- https://doi.org/10.1136/gut.39.6.811
Abstract
BACKGROUND: Coeliac disease (CD) mucosa is flattened despite epithelial hyperproliferation. AIMS: To establish mechanisms of cell loss in CD. PATIENTS: 14 controls, 17 active CD patients, and 16 maintained with gluten free diet. METHODS: Programmed cell death was examined in small intestinal biopsy specimens by staining fragmented DNA using terminal uridine deoxynucleotidyl nick end labelling (TUNEL), in comparison with haematoxylin and eosin stained adjacent sections. Double staining with anti-CD45 antibodies determined the origin of apoptotic cells. Apoptosis was graded from 1-3 (< 5, 5-20, > 20% respectively). Proliferating cells, immunostained by Ki-67 (MIB-1) antibody, were counted. RESULTS: Apoptotic cells were seen rarely by haematoxylin and eosin but more readily by TUNEL. In controls, 1.4 +/- 0.2% of epithelial cells were apoptotic (mean grade 1.1), mainly located in the upper villus. In active CD, frequent apoptotic cells were distributed throughout the crypt-villus unit (mean grade 2.4), decreasing after treatment to 1.1 (p < 0.001) even when still histologically abnormal. CD45 antibodies rarely stained apoptotic cells in active CD. The number of TUNEL positive cells correlated with proliferating cell number (p < 0.001). CONCLUSION: Enterocyte apoptosis is greatly increased in untreated CD, correlates with proliferation, and falls to normal with a gluten free diet, before histological improvement. Increased apoptosis may be responsible for villous atrophy in CD.Keywords
This publication has 28 references indexed in Scilit:
- Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma.Gut, 1995
- Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge.Gut, 1995
- manipulation of cell death — the development of novel strategies for the treatment of gastrointestinal diseaseAlimentary Pharmacology & Therapeutics, 1995
- Apoptosis in the Pathogenesis and Treatment of DiseaseScience, 1995
- A possible explanation for the differential cancer incidence in the intestine, based on distribution of the cytotoxic effects of carcinogens in the murine large bowelCarcinogenesis: Integrative Cancer Research, 1992
- Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.The Journal of cell biology, 1992
- Quantitative study of apoptosis in normal rat gastroduodenal mucosaJournal of Gastroenterology and Hepatology, 1990
- Ultrastructure of cell loss in intestinal mucosaJournal of Ultrastructure Research, 1977
- Gastro-Intestinal Cell Loss in ManDigestion, 1973
- Dynamics of the mucosa of the small intestine in idiopathic steatorrhoeaGut, 1962