Tropical enteropathy : a T-cell-mediated crypt hyperplastic enteropathy

Tropical enteropathy is widespread throughout the tropics, but its pathogenesis is unknown. T-cell activation has been demonstrated to result in enteropathy in vitro and in animal models, and occurs in untreated patients with coeliac disease. We have therefore examined the hypothesis that T-cell activation is important in the pathogenesis of tropical enteropathy. Healthy black Zambian subjects were compared with black and white South Africans. Quantitative microscopy was conducted on distal duodenal biopsies. Mucosal T-cell activation was quantitated by dual colour immunofluorescence staining for CD3 plus CD69 or HLA-DR. Crypt proliferation was measured by direct counting of Feulgen-stained mitotic figures, and systemic immune activation by assay of serum tumour necrosis factor alpha (TNF-alpha). Villous height was reduced (P = 0.0004), crypt depth increased (P < 0.0001), and mitoses per crypt increased (P = 0.014) in black Zambians compared with black and white South Africans. Mucosal thickness was similar. Intraepithelial lymphocyte count was increased in the black groups compared with whites (P = 0.03). CD3+CD69+ (P = 0.0007) and CD3+HLA-DR+ (P < 0.0001) expression was increased in black Zambians compared with black and white South Africans. Serum TNF-alpha was similar in all groups. Tropical enteropathy is associated with mucosal T-cell activation and crypt hyperplasia. Tropical enteropathy occurs in the absence of malnutrition, diarrhoea or systemic illness.