X-Linked Syndrome Enteropathy Polyendocrinopathy Immune Dysregulation

An X-linked recessive immunologic disorder characterized by onset in infancy of severe diarrhea due to enteropathy, type 1 diabetes mellitus, and DERMATITIS. Other features may include HYPOTHYROIDISM; AUTOIMMUNE HEMOLYTIC ANEMIA; THROMBOCYTOPENIA; LYMPHADENOPATHY; HEPATITIS, and NEPHRITIS. The disorder may be fatal before age 2 years if not aggressively treated. Mutations in the FOXP3 gene have been identified. OMIM: 304790

Also Known As:

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome; Autoimmunity-Immunodeficiency Syndrome, X-Linked; Diabetes Mellitus, Congenital Insulin-Dependent, with Fatal Secretory Diarrhea; Diarrhea, Polyendocrinopathy, Fatal Infection Syndrome, X-Linked; Enteropathy, Autoimmune, with Hemolytic Anemia and Polyendocrinopathy; IDDM-Secretory Diarrhea Syndrome; Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked; Ipex Syndrome; Polyendocrinopathy, Immune Dysfunction, and Diarrhea, X-Linked; X-Linked Autoimmunity-Allergic Dysregulation Syndrome

Networked: 101 relevant articles (4 outcomes, 4 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Autoimmune Lymphoproliferative Syndrome
2.	Autoimmune Polyendocrinopathies (Schmidt Syndrome)
3.	Eczema
4.	Autoimmune Diseases (Autoimmune Disease)
5.	Autoimmune enteropathy

Experts

1.	Bacchetta, Rosa: 9 articles (01/2020 - 12/2008)
2.	Passerini, Laura: 8 articles (01/2020 - 12/2008)
3.	Kobayashi, Ichiro: 7 articles (01/2022 - 10/2011)
4.	Torgerson, Troy R: 7 articles (01/2022 - 09/2006)
5.	Ochs, Hans D: 7 articles (06/2020 - 08/2005)
6.	Kanegane, Hirokazu: 5 articles (01/2022 - 06/2009)
7.	Gambineri, Eleonora: 4 articles (01/2015 - 05/2007)
8.	Hoshino, Akihiro: 3 articles (01/2022 - 01/2019)
9.	Chatila, Talal A: 3 articles (01/2021 - 07/2007)
10.	Ruemmele, Frank M: 3 articles (01/2021 - 08/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to X-Linked Syndrome Enteropathy Polyendocrinopathy Immune Dysregulation:

1.	AutoantibodiesIBA 12/01/2018 - "We also identified autoantibodies to COL17 and BP230 in patients with IPEX syndrome and found an association between production of autoantibodies to COL17 and an eczematous skin phenotype. " 06/18/2015 - "Following immune reconstitution of this novel strain with HSCs from a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, associated with aberrant FOXP3 function, mice developed a lethal inflammatory disorder with multiorgan involvement and autoantibody production mimicking the pathology seen in affected humans. " 11/01/2010 - "In this case series we evaluated serum samples from 12 patients with IPEX syndrome for the presence of common autoantibodies associated with a broad range of autoimmune disorders. " 11/01/2010 - "The spectrum of autoantibodies in IPEX syndrome is broad and includes anti-mitochondrial autoantibodies." 01/01/2019 - "Clinical manifestations of IPEX syndrome are characterized by various autoimmune diseases with autoantibodies. "
2.	villinIBA 02/01/2014 - "Improvement in clinical symptoms was correlated with expansion of donor-derived Tregs and disappearance of anti-villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. " 01/01/2013 - "Autoantibodies to harmonin and villin are diagnostic markers in children with IPEX syndrome." 10/01/2011 - "We conclude that both AIE-75 and villin appear to be brush border autoantigens in IPEX syndrome and could be used for the diagnosis of AIE in patients with presumptive IPEX syndrome." 01/01/2015 - "However, to date, anti-AIE-75 and anti-villin antibodies or anti-TPH-1 antibodies have not been tested in APECED or IPEX syndrome, respectively. " 10/01/2011 - "Four of five sera from patients with IPEX syndrome reacted with a fusion protein of glutathione-S-transferase and full length villin (GST-villin), whereas only three of 98 control sera weakly reacted with GST-villin. "
3.	dupilumabIBA 01/01/2022 - "Case report: Dupilumab treatment improved type 2 disorders in a patient with IPEX syndrome diagnosis." 01/01/2022 - "We described a case of IPEX syndrome successfully controlled with dupilumab, an anti-IL4 receptor alpha subunit inhibitor. " 09/01/2021 - "This is the first known report of dupilumab being used in a patient with IPEX syndrome." 09/01/2021 - "Generalized eczematous dermatitis and pruritus responsive to dupilumab in a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome."
4.	AutoantigensIBA 12/01/2018 - "Sera and skin from scurfy mice and sera from patients with IPEX syndrome were analyzed to detect target autoantigens by using immunofluorescence studies, ELISAs, and immunoblotting. " 12/01/2018 - "We sought to elucidate the target autoantigens in the skin under the condition of Treg cell dysfunction caused by forkhead box P3 (Foxp3) gene mutations in scurfy mice and patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. " 03/01/2017 - "Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. " 10/01/2011 - "We conclude that both AIE-75 and villin appear to be brush border autoantigens in IPEX syndrome and could be used for the diagnosis of AIE in patients with presumptive IPEX syndrome." 10/01/2011 - "Although autoimmune enteropathy (AIE)-related 75 kDa antigen (AIE-75) is a prominent autoantigen involved in the enteropathy associated with IPEX syndrome, some patients with this syndrome demonstrated autoantibody recognizing a 95 kDa protein rather than AIE-75 in the small intestine. "
5.	Protein Isoforms (Isoforms)IBA 01/01/2022 - "In this study, we show that patients expressing only the shorter isoform fail to maintain self-tolerance and develop immunodeficiency, polyendocrinopathy, and enteropathy X-linked (IPEX) syndrome. " 01/01/2019 - "The FOXP3Δ2 isoform supports Treg cell development and protects against severe IPEX syndrome."
6.	Interleukin-2 Receptors (IL 2 Receptor)IBA 12/01/2005 - "Recent studies of autoimmune polyendocrinopathy syndrome type 1, autoimmune lymphoproliferative syndrome, immunodysregulation, polyendocrinopathy and enteropathy, X-linked, IL-2 receptor alpha-chain deficiency, and, in particular, their corresponding mouse models, have revealed the details of the molecular mechanisms of normal immune tolerance, and exposed how defects in these mechanisms result in human autoimmunity. " 01/01/2015 - "They include immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, which is caused by mutations in forkhead box P3 (FOXP3), and IPEX-like disorders caused by mutations in IL-2 receptor α (IL2RA), signal transducer and activator of transcription 5b (STAT5b), and signal transducer and activator of transcription 1 (STAT1). "
7.	Codon (Codons)IBA 01/01/2011 - "Diagnostic studies revealed a one-codon deletion in the FoxP3 gene, which led to the diagnosis of immune dysregulation polyendocrinopathy, enteropathy X-linked syndrome. "
8.	Forkhead Transcription Factors (Forkhead Box Proteins)IBA 01/01/2022 - "Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare X-linked recessive immunodeficiency caused by mutations in the forkhead box protein 3 (FOXP3) gene. " 05/01/2021 - "Immune dysregulation, polyendocrinopathy and enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by loss-of-function mutations in the gene forkhead box protein 3 (FOXP3). " 01/01/2021 - "(1) Background: IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome characterizes a complex autoimmune reaction beginning in the perinatal period, caused by a dysfunction of the transcription factor forkhead box P3 (FOXP3). " 05/26/2020 - "Immune dysregulation, polyendocrinopthy, enteropathy, X-linked (IPEX) syndrome is a rare X-linked recessive disease caused by mutations in the forkhead box protein 3 (FOXP3) gene, which is a master transcriptional regulator for the development and function of CD4+CD25+ regulatory T (Treg) cells. " 01/01/2020 - "IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. "
9.	Transcription Factors (Transcription Factor)IBA 11/23/2023 - "FOXP3 gene is a key transcription factor driving immune tolerance and its deficiency causes immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome (IPEX), a prototypic primary immune regulatory disorder (PIRD) with defective regulatory T (Treg) cells. " 01/01/2023 - "Mutations of the transcription factor FoxP3 in patients with "IPEX" (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) disrupt regulatory T cells (Treg), causing an array of multiorgan autoimmunity. " 10/01/2020 - "Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare monogenic primary immunodeficiency due to mutations of FOXP3, a master transcription factor of regulatory T cells (Treg). " 06/01/2020 - "Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder characterized by early onset fatal multi-system autoimmunity due to loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor which is crucial for the development, maturation, and maintenance of CD4+ regulatory T (T-reg) cells. " 01/01/2020 - "Immune-dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a lethal disease caused by mutations in a transcription factor critical for the function of thymus-derived regulatory T (Treg) cells (ie, FOXP3), resulting in impaired Treg function and autoimmunity. "
10.	Proteins (Proteins, Gene)FDA Link 01/01/2022 - "At the age of 14 years, the patient was diagnosed with IPEX syndrome due to a c.748-750del (p.Lys250del) mutation in the leucine zipper domain of the FOXP3 protein. " 01/01/2019 - "We identified an IPEX (immune dysregulation polyendocrinopathy enteropathy X-linked) syndrome patient with a FOXP3 mutation in the domain swap interface of the protein. " 12/01/2008 - "Therefore genetic analysis of FOXP3 should always be performed to ensure an accurate diagnosis, and FOXP3 protein expression analysis should not be the only diagnostic tool for IPEX syndrome." 12/01/2008 - "In 14 unrelated affected male subjects who were given diagnoses of IPEX syndrome based on FOXP3 gene sequencing, we determined whether particular FOXP3 mutations affected FOXP3 protein expression and correlated the molecular and clinical data. " 03/01/2007 - "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. "

Therapies and Procedures

1.	Hematopoietic Stem Cell Transplantation 10/01/2020 - "Currently hematopoietic stem cell transplantation represents the only known effective cure for IPEX syndrome. " 01/01/2012 - "The only known effective cure for IPEX syndrome is hematopoietic stem cell transplantation, but it is always limited by the availability of a suitable donor and the lack of specific guidelines for bone marrow transplant in the context of this disease. " 01/01/2017 - "Finally, the boy was diagnosed as IPEX syndrome by genetic test and received hematopoietic stem cell transplantation (HSCT). " 01/01/2015 - "Gut immune reconstitution in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome after hematopoietic stem cell transplantation." 05/28/2009 - "Selective engraftment of donor CD4+25high FOXP3-positive T cells in IPEX syndrome after nonmyeloablative hematopoietic stem cell transplantation."
2.	Therapeutics 05/01/2014 - "Specifically, anti-CD4 therapy is expected to fail in patients suffering from the IPEX syndrome due to the lack of functional Foxp3(+) Tregs. " 05/01/2010 - "This Review discusses the genetic basis of APS-1, APS-2 and IPEX syndrome, with an emphasis on the mechanisms of autoimmunity and presents currently available therapies to treat their underlying autoimmune disorders." 01/01/2020 - "At present, hematopoietic stem cell transplantation is the therapy of choice for patients with IPEX syndrome. " 11/01/2019 - "Presently, allogeneic hematopoietic stem cell transplantation (HSCT) is a potential curative therapy for IPEX syndrome, but not for T1D. " 01/01/2021 - "Our data suggest an association between the gut microbiota and clinical symptoms of patient with IPEX syndrome and demonstrate FMT as an alternative therapy for severe diarrhea unresponsive to routine therapy in these patients."
3.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 02/01/2014 - "Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome." 01/01/2009 - "FOXP3 expression following bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning." 01/01/2007 - "Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning." 06/07/2001 - "Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) by allogeneic bone marrow transplantation." 06/01/2005 - "One underwent total colectomy and bone marrow transplantation and one developed an IPEX syndrome. "
4.	Stem Cell Transplantation 03/01/2016 - "A challenging undertaking: Stem cell transplantation for immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome." 11/01/2019 - "Successful Salvage Haploidentical Alpha-Beta T Cell-Depleted Stem Cell Transplantation After Busulfan-Based Myeloablation in a Patient With IPEX Syndrome: A Case Report."
5.	Transplantation 04/01/2008 - "Immune reconstitution and recovery of FOXP3 (forkhead box P3)-expressing T cells after transplantation for IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome." 01/01/2007 - "Submyeloablative cord blood transplantation corrects clinical defects seen in IPEX syndrome."