title: 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.
authors: Division of Allergy and Immunology, Department of Pediatrics, University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. heltzer@email.chop.edu
authors: Meredith Lee
authors: ML
authors: Heltzer
authors: John K
authors: JK
authors: Choi
authors: Hans D
authors: HD
authors: Ochs
authors: Kathleen E
authors: KE
authors: Sullivan
authors: Troy R
authors: TR
authors: Torgerson
authors: Linda M
authors: LM
authors: Ernst
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004724:Endoscopy; D017809:Fatal Outcome; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007420:Intestine, Large / Q000601:surgery; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy; D011504:Protein-Losing Enteropathies / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use; D013577:Syndrome; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D020123:Sirolimus