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.
MeSH terms
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Case-Control Studies
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Child
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Child, Preschool
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Endoscopy
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Fatal Outcome
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Follow-Up Studies
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Forkhead Transcription Factors* / genetics
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Forkhead Transcription Factors* / metabolism
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Frameshift Mutation
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Genetic Diseases, X-Linked / diagnosis*
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Genetic Diseases, X-Linked / genetics
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Genetic Diseases, X-Linked / immunology
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Genetic Diseases, X-Linked / pathology
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Genetic Diseases, X-Linked / surgery
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Genetic Diseases, X-Linked / therapy
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Genetic Testing*
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Humans
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Immunohistochemistry
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Immunosuppressive Agents / therapeutic use
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / pathology
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Intestine, Large / surgery
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Male
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Mucous Membrane / metabolism
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Mucous Membrane / pathology
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Mutation, Missense
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Polyendocrinopathies, Autoimmune / diagnosis*
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Polyendocrinopathies, Autoimmune / genetics
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Polyendocrinopathies, Autoimmune / immunology
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Polyendocrinopathies, Autoimmune / pathology
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Polyendocrinopathies, Autoimmune / surgery
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Polyendocrinopathies, Autoimmune / therapy
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Protein-Losing Enteropathies / diagnosis*
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Protein-Losing Enteropathies / genetics
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Protein-Losing Enteropathies / immunology
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Protein-Losing Enteropathies / pathology
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Protein-Losing Enteropathies / surgery
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Protein-Losing Enteropathies / therapy
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Retrospective Studies
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Sirolimus / therapeutic use
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Syndrome
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T-Lymphocytes / metabolism
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Time Factors
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Treatment Outcome
Substances
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FOXP3 protein, human
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Forkhead Transcription Factors
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Immunosuppressive Agents
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Sirolimus