Mucosal regulatory and effector T-cell imbalance in CVID-associated enteropathy.

Background: Common variable immunodeficiency (CVID) frequently presents with gastrointestinal complications, yet the immunopathogenesis of CVID-associated enteropathy remains poorly understood. Objective: This study aimed to investigate intestinal T cell subset distributions and intracellular cytokine profiles in order to better understand mucosal immune alterations associated with enteropathy in CVID. Methods: Duodenal and ileal biopsy specimens were obtained from CVID patients with enteropathy (EP, n=11) and without enteropathy (EN, n=13), patients with Crohn's disease (CD, n=9), and healthy controls (HC, n=14). Lamina propria mononuclear cells were isolated and analyzed by flow cytometry to determine T-cell phenotypes, maturation status, and intracellular cytokine production following stimulation. Results: Duodenal tissue from EP patients showed significantly reduced frequencies of total T, cytotoxic T, mucosal T, mucosal cytotoxic T, accompanied by an expansion of γδ T cells and a trend toward reduced Treg frequencies. Intracellular IL-17 production was markedly decreased in both mucosal and γδ T cell subsets. In the ileum, EP patients displayed reduced Treg frequencies together with increased γδ T cells and enhanced IFN-γ production by γδ T cells. Conclusions: This study identifies distinct, compartment-specific alterations in duodenal and ileal T cell profiles in CVID-associated enteropathy. Reduced IL-17 production and γδ T cell expansion in the duodenum, together with reduced Treg frequencies and increased IFN-γ-producing γδ T cells in the ileum, characterized CVID-associated enteropathy. These findings indicate disrupted mucosal immune homeostasis and provide a basis for future longitudinal and mechanistic studies.