Mapping and Characterization of Isolated Lymphoid Follicles in Patients with Hirschsprung-Associated Enterocolitis

Hirschsprung-associated enterocolitis (HAEC) is a severe complication of Hirschsprung's disease (HSCR), but its pathogenesis remains unclear. Gut-associated lymphoid tissue (GALT), including isolated lymphoid follicles (ILFs), plays a key role in mucosal immunity. This study investigated the presence, distribution, and phenotype of ILFs in colonic tissue from 35 HSCR patients and 12 controls. Histological and immunohistochemical analyses revealed mature ILFs in both ganglionic and aganglionic bowel, with no significant differences in densities between HSCR patients with and without HAEC. However, patients that developed HAEC showed signs of enhanced B-cell activation in ILFs. Patients with a stoma had significantly increased ILF density, suggesting that luminal content may influence ILF development. Despite the absence of enteric neurons, ILFs were structurally similar to those described in adults, indicating that ILF formation occurs independently of a functional enteric nervous system. These findings provide new insights into mucosal immunity in HSCR and suggest a role for activation of the mucosal B-cell compartment in HAEC pathogenesis.