TPN(nutritional purpose), Cyclosporin A and FK506, Bone marrow transplant[2][3]
IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked) syndrome is a rare disease linked to the dysfunction of the transcription factor FOXP3, widely considered to be the master regulator of the regulatory T cell lineage.[4][5] It leads to the dysfunction of regulatory T-cells and the subsequent autoimmunity.[6] The disorder manifests with autoimmune enteropathy, psoriasiform or eczematous dermatitis, nail dystrophy, autoimmune endocrinopathies, and autoimmune skin conditions such as alopecia universalis and bullous pemphigoid.[6][7]
Management for immunodysregulation polyendocrinopathy enteropathy X-linked syndrome has seen limited success in treating the syndrome by bone marrow transplantation.[8]
Contents
1Symptoms and signs
2Genetics
3Mechanism
4Diagnosis
5Treatment
6See also
7References
8Further reading
9External links
Symptoms and signs
Eczema
Some of the symptoms and signs of IPEX syndrome are the following:[7]
Lymphadenopathy
Eczema
Hypothyroidism
Diarrhea
Genetics
Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome is inherited in males via an x-linked recessive manner. Apparently the FOXP3 gene, whose cytogenetic location is Xp11.23, is involved in the mechanism of this condition.[4][5]
Mechanism
This autoimmunity called IPEX is an attack from the body's own immune system against the body's own tissues and organs.[3] Early age onset of this disease in males causes severe enlargement of the secondary lymphoid organs, and insulin dependent diabetes[medical citation needed]
This condition indicates the loss of CD4+CD25+ T regulatory cells, and express the transcription factor Foxp3. Foxp3 decrease is a consequence of unchecked T cell activation, which is secondary to loss of regulatory T cells.[9]
Diagnosis
The diagnosis of immunodysregulation polyendocrinopathy enteropathy X-linked syndrome is consistent with the following criteria:[1]
Clinical examination
Family history
Laboratory findings
Genetic testing
Treatment
FK506(Tacrolimus)
In terms of treatment the following are done to manage the IPEX syndrome in those affected individuals (corticosteroids are the first treatment that is used):[3][2]
TPN (nutritional purpose)
Cyclosporin A and FK506
Sirolimus (should FK506 prove non-effective)
Granulocyte colony stimulating factor
Bone marrow transplant
Rituximab
See also
Autoimmune polyendocrine syndrome
FOXP3
Autoimmune polyendocrine syndrome type 2
References
^ abcRESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Immune dysregulation polyendocrinopathy enteropathy X linked syndrome". www.orpha.net. Retrieved 2017-04-18.
^ abEisenbarth, George S. (2010-12-13). Immunoendocrinology: Scientific and Clinical Aspects. Springer Science & Business Media. pp. 129–138. ISBN 9781603274784.
^ abcHannibal, Mark C.; Torgerson, Troy (1993-01-01). "IPEX Syndrome". In Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Ledbetter, Nikki; Mefford, Heather C. GeneReviews(®). Seattle (WA): University of Washington, Seattle. PMID 20301297.update 2011
^ abReference, Genetics Home. "IPEX syndrome". Genetics Home Reference. Retrieved 2017-04-16.
^ abReference, Genetics Home. "FOXP3 gene". Genetics Home Reference. Retrieved 2017-04-16.
^ abRapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 72. ISBN 978-1-4160-2999-1.
^ ab"Immunodysregulation, polyendocrinopathy and enteropathy X-linked | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-04-16.
^Wildin RS, Smyk-Pearson S, Filipovich AH (August 2002). "Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome". J Med Genet. 39 (8): 537–45. doi:10.1136/jmg.39.8.537. PMC 1735203. PMID 12161590.
^Verbsky, James W.; Chatila, Talal A. (2017-04-18). "Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) and IPEX-Related Disorders: an Evolving Web of Heritable Autoimmune Diseases". Current Opinion in Pediatrics. 25 (6): 708–714. doi:10.1097/MOP.0000000000000029. ISSN 1040-8703. PMC 4047515. PMID 24240290.
Further reading
Bacchetta, Rosa; Barzaghi, Federica; Roncarolo, Maria-Grazia (25 February 2016). "From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation". Annals of the New York Academy of Sciences. 1417 (1): 5–22. doi:10.1111/nyas.13011. ISSN 1749-6632. PMID 26918796.
Barzaghi, Federica; Passerini, Laura; Bacchetta, Rosa (1 January 2012). "Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A Paradigm of Immunodeficiency with Autoimmunity". Frontiers in Immunology. 3: 211. doi:10.3389/fimmu.2012.00211. ISSN 1664-3224. PMC 3459184. PMID 23060872.
Elzouki, A. Y.; Harfi, H. A.; Nazer, H.; Stapleton, F. B.; Oh, William; Whitley, R. J. (2012-01-10). Textbook of Clinical Pediatrics. Springer Science & Business Media. ISBN 9783642022029.
External links
Classification
D
ICD-10: E31.0
OMIM: 304790
DiseasesDB: 33417
External resources
GeneReviews: IPEX Syndrome
Orphanet: 37042
PubMed
v
t
e
Sex linkage: X-linked disorders
X-linked recessive
Immune
Chronic granulomatous disease (CYBB)
Wiskott–Aldrich syndrome
X-linked severe combined immunodeficiency
X-linked agammaglobulinemia
Hyper-IgM syndrome type 1
IPEX
X-linked lymphoproliferative disease
Properdin deficiency
Hematologic
Haemophilia A
Haemophilia B
X-linked sideroblastic anemia
Endocrine
Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy
Lentiviral vectors for the treatment of primary immunodeficiencies.
Farinelli G1, Capo V, Scaramuzza S, Aiuti A.Author information 1Department of Pediatrics, Children's Hospital Bambino Gesù and University of Rome Tor Vergata School of Medicine, Rome, Italy.AbstractIn the last years important progress has been made in the treatment of several primary immunodeficiency disorders (PIDs) with gene therapy. Hematopoietic stem cell (HSC) gene therapy indeed represents a valid alternative to conventional transplantation when a compatible donor is not available and recent success confirmed the great potential of this approach. First clinical trials performed with gamma retroviral vectors were promising and guaranteed clinical benefits to the patients. On the other hand, the outcome of severe adverse events as the development of hematological abnormalities highlighted the necessity to develop a safer platform to deliver the therapeutic gene. Self-inactivating (SIN) lentiviral vectors (LVVs) were studied to overcome this hurdle through their preferable integration pattern into the host genome. In this review, we describe the recent advancements achieved both in vitro and at preclinical level with LVVs for the treatment of Wiskott-Aldrich syndrome (WAS), chronic granulomatous disease (CGD), ADA deficiency (ADA-SCID), Artemis deficiency, RAG1/2 deficiency, X-linked severe combined immunodeficiency (γchain deficiency, SCIDX1), X-linked lymphoproliferative disease (XLP) and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.
Journal of inherited metabolic disease.J Inherit Metab Dis.2014 Mar 12. [Epub ahead of print]
In the last years important progress has been made in the treatment of several primary immunodeficiency disorders (PIDs) with gene therapy. Hematopoietic stem cell (HSC) gene therapy indeed represents a valid alternative to conventional transplantation when a compatible donor is not available and re
Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome.
Horino S1, Sasahara Y, Sato M, Niizuma H, Kumaki S, Abukawa D, Sato A, Imaizumi M, Kanegane H, Kamachi Y, Sasaki S, Terui K, Ito E, Kobayashi I, Ariga T, Tsuchiya S, Kure S.Author information 1Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; Department of Hematology and Oncology, Miyagi Children's Hospital, Sendai, Miyagi, Japan.AbstractIPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA-matched sibling donor. We could achieve engraftment and regimen-related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. 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. This clinical observation suggests that donor-derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.
Pediatric transplantation.Pediatr Transplant.2014 Feb;18(1):E25-30. doi: 10.1111/petr.12184. Epub 2013 Nov 7.
IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA-matched sibling donor. We could achieve engr
Quantitative polyadenylation site mapping with single-molecule direct RNA sequencing.
Ozsolak F.Author information Helicos BioSciences Corporation, One Kendall Square, Cambridge, MA, 02139, USA, fatihozsolak@gmail.com.AbstractThe known regulatory role of 3' untranslated regions (3'UTRs) and poly(A) tails in RNA localization, stability, and translation, and polyadenylation regulation defects leading to human diseases such as oculopharyngeal muscular dystrophy, thalassemias, thrombophilia, and IPEX syndrome underline the need to fully characterize genome-wide polyadenylation states and mechanisms across normal physiological and disease states. This chapter outlines the quantitative polyadenylation site mapping and analysis strategies developed with the single-molecule direct RNA sequencing technology.
Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2014;1125:145-55. doi: 10.1007/978-1-62703-971-0_13.
The known regulatory role of 3' untranslated regions (3'UTRs) and poly(A) tails in RNA localization, stability, and translation, and polyadenylation regulation defects leading to human diseases such as oculopharyngeal muscular dystrophy, thalassemias, thrombophilia, and IPEX syndrome underline the n
Genetic counseling. IPEX syndrome is inherited in an X-linked manner. The risk to sibs of the proband depends on the carrier status of the mother. If the mother of the proband is a carrier, the chance of transmitting the disease ...
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is characterized by the development of multiple autoimmune disorders in affected individuals. Autoimmune disorders occur when the immune system ...
