title: From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation.
abstract: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder that increasingly has gained attention as a model of genetic autoimmunity. Numerous papers documenting the key clinical and molecular characteristics of IPEX have provided a detailed understanding of this devastating disease. IPEX is a primary immunodeficiency caused by mutations in the gene FOXP3, which encodes an essential transcription factor required for maintenance of thymus-derived regulatory T (tTreg) cells. tTregcell dysfunction is the main pathogenic event leading to multiorgan autoimmunity in IPEX. In addition to the traditional clinical presentation (i.e., severe enteropathy, type 1 diabetes, and eczema), IPEX may encompass other variable and distinct clinical manifestations. As IPEX awareness and characterization have increased, so has identification of FOXP3 mutations, with at least 70 to date. Thus, while FOXP3 is the unifying gene, IPEX is a complex and diverse clinical continuum of disorders. Despite understanding IPEX pathogenesis, new treatment options have remained elusive, although early diagnosis led to hematopoietic stem cell transplantation (HSCT) and immunosuppression treatment and improved patient outcomes. Here, we review current knowledge about IPEX syndrome and highlight findings that could lead to novel targeted treatments.
authors.affiliation: Department of Pediatrics, Division of Pediatric Stem Cells, Transplantation and Regenerative Medicine, Stanford University Medical School, Stanford, California.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bacchetta
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Barzaghi
authors.affiliation: Department of Pediatrics, Division of Pediatric Stem Cells, Transplantation and Regenerative Medicine, Stanford University Medical School, Stanford, California.
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Roncarolo
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000151:congenital* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D003967:Diarrhea / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007154:Immune System Diseases / Q000151:congenital* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D007165:Immunosuppression Therapy; D007231:Infant, Newborn; D008297:Male; D008957:Models, Genetic; D018448:Models, Immunological; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D000072417:Protein Domains; D012045:Regulatory Sequences, Nucleic Acid; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: FOXP3; HSCT; IPEX; Treg; autoimmune enteropathy; neonatal diabetes; primary immunodeficiency