A potential screening tool for IPEX syndrome.
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.
Heltzer
Meredith Lee
ML
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
Choi
John K
JK
Ochs
Hans D
HD
Sullivan
Kathleen E
KE
Torgerson
Troy R
TR
Ernst
Linda M
LM
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
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D020123:Sirolimus