Increased small intestinal apoptosis in coeliac disease

被引:138
作者
Moss, SF
Attia, L
Scholes, JV
Walters, JRF
Holt, PR
机构
[1] ST LUKES ROOSEVELT HOSP,DEPT MED,DIV GASTROENTEROL,NEW YORK,NY 10025
[2] COLUMBIA UNIV,NEW YORK,NY
[3] NYU,SCH MED,DEPT PATHOL,NEW YORK,NY
[4] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT MED,LONDON,ENGLAND
关键词
coeliac sprue; gluten sensitive enteropathy; programmed cell death; cell proliferation; apoptosis;
D O I
10.1136/gut.39.6.811
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:811 / 817
页数:7
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