Objective: 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.
Patients and methods: 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).
Results: 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.
Conclusions: Tropical enteropathy is associated with mucosal T-cell activation and crypt hyperplasia. Tropical enteropathy occurs in the absence of malnutrition, diarrhoea or systemic illness.