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

Common variable immunodeficiency (CVID) frequently presents with gastrointestinal complications, yet the immunopathogenesis of CVID-associated enteropathy remains poorly understood.

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.

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.

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.

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.