A Potential Screening Tool for IPEX Syndrome

Abstract

IPEX syndrome is a rare, inherited condition characterized by immune dysfunction, polyendocrinopathy, enteropathy, and X-linked recessive inheritance. Patients typically present in infancy with severe diarrhea and failure to thrive. Most children die by 1 year of age without therapy. The diagnosis is established by genetic analysis, which often takes several weeks to complete and can sometimes delay crucial immunosuppressive treatment. We attempted to develop a screening tool that allows rapid identification of patients with IPEX syndrome using immunocytochemical staining of FOXP3+ cells in bowel biopsies. We found that 2 patients with classic IPEX syndrome due to protein-truncating mutations in FOXP3 had markedly decreased staining of FOXP3+ T cells in the lamina propria and lymphoid aggregates. One patient with a mild, late-onset presentation and a missense mutation in FOXP3 had intact staining of FOXP3+ cells. This screening test provides a valuable tool for diagnosing IPEX syndrome in extremely ill patients who may not tolerate a delay in therapeutic intervention.