Enhanced local immune response in children with prolonged gastrointestinal symptoms

Aim: Recently, we reported typical endoscopic findings and an increment in gammadelta(+) T cells in the foregut among children with food-sensitive enteropathy other than coeliac disease. To find out the extend to which the upregulation of the local immune response might explain gastrointestinal (GI) complaints of the foregut, we sought to examine by the increment in gammadelta(+) T cells a 1-y consecutive series of children referred for recurrent GI complaints to a tertiary-level hospital. Methods: A 1-y cohort of 102 children scheduled for gastroduodenoscopy were examined for mucosal histology and the densities of CD3(+), alphabeta(+) and gammadelta(+) T-cell subsets from mid-duodenal specimens. The final diagnostic categories were used in analysing the data. Results: Fifteen subjects showed villous atrophy and a high gammadelta(+) T-cell density; the finding being compatible with coeliac disease ( CD). At the other extreme, 20 subjects in whom diagnostic GI diseases were ruled out showed low densities and served as controls. The subjects reporting GI symptoms after an open food challenge with milk and/or cereals (n = 18) as well as children remitting with a milk- or cereal-eliminating diet but not responding to a challenge ( n = 23) also expressed significantly higher densities of gammadelta(+) T cells than the controls. In all, 45 of 102 children could be considered to have an elevated gammadelta(+) T-cell density as an indication of locally activated immune response. Lack of villous architecture and lymphonodular hyperplasia of the duodenal bulb as an endoscopic finding and atopic dermatitis but not the presence of DQ2 alleles showed a close association with these increased densities. Conclusion: Considering that an elevated incidence of gammadelta(+) T cells is an indication of mucosal response against luminal antigens, up to half the children with prolonged GI symptoms have immune mediated disorder; CD and food allergy being the most obvious clinical entities.