Lymphonodular hyperplasia of the terminal ileum associated with colitis shows an increased γδ + T-cell density in children

Abstract

OBJECTIVE: Recently we reported a close association between lymphonodular hyperplasia (LNH) of the bulb of the duodenum and increased densities of intraepithelial γδ + T-cells in subjects with untreated food allergies. In this study we sought to determine whether children with LNH of the terminal ileum (TI) show a similar correlation. METHODS: The mucosal specimens taken by colonoscopy from the TIs of 22 children with LNH of the TI without colitis, 13 with right-sided colitis or pancolitis, nine with left-sided colitis, eight with Crohn’s disease, and three endoscopically healthy subjects were studied for T-cell subsets with monoclonal antibodies using a three-layer peroxidase staining method. RESULTS: LNH of the TI was found in 32 of the 55 subjects (58%). In 22 it was the only endoscopic finding, but in nine of 13 subjects (69%) it was related to right-sided colitis or pancolitis. In patients with left-sided colitis or Crohn’s disease it was diagnosed only rarely. In the whole study population, LNH of the TI showed a significant association with the increment in the density of γδ + T-cells. The subjects with LNH of the TI and colitis starting from the cecum showed the highest values, discriminating them statistically from any other study group. Accordingly their γδ +/CD3 + ratio was high. Even in the subjects with LNH of the TI without colitis, the increment in γδ + T-cells was significant as compared with the subjects with left-sided colitis. Upregulations of D-related expression on the mucosa of the TI were similar regardless of the presence of LNH or colitis or an increment in γδ + T-cells. CONCLUSION: Our preliminary observations showed increased densities of intraepithelial γδ + T-cells and elevated γδ +/CD3+ ratios in subjects with LNH on the mucosa of the TI, especially if related to colitis starting at the cecum, but not in subjects with typical left-sided colitis or granulomatous Crohn’s disease. The study also provides further evidence suggesting the significance of food-borne antigens in the pathogenetic mechanism of right-sided colitis or pancolitis. The finding also indicates the significance of classifying colitis into γδ-positive and -negative diseases, and has implications for the treatment of these entities.