Prospective immunological profiling in a case of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)

IPEX syndrome is a genetic autoimmune disease characterized by immune-mediated polyendocrinopathy, enteropathy, and X-linked inheritance. We describe a case of IPEX in which lymphocyte phenotypes were assessed at birth, before initiation of Cyclosporin A therapy, and at frequent intervals to 18 months of age. We performed flow cytometry for lymphocyte subtypes and for activation markers (HLA-DR, CD25, and CD69 or CD71). The ratios of both T to B cells and CD4+ to CD8+ cells were elevated at birth, but CD4+ cells were not activated. HLA-DR+ and CD25+ activated T-cells increased in association with two episodes of clinical deterioration: colitis and the onset of type I diabetes mellitus. These results indicate that measures of activation, particularly HLA-DR+ and CD25+ frequency, correlate well with the development of early active disease and may presage clinical episodes. Continuous maintenance of immunosuppression, once started, appears critical for prevention of permanent tissue damage.