Document Detail


Autoimmune polyglandular syndromes.
MedLine Citation:
PMID:  20309000     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The autoimmune polyglandular syndromes-a group of syndromes comprising a combination of endocrine and nonendocrine autoimmune diseases-differ in their component diseases and in the immunologic features of their pathogenesis. One of the three main syndromes, type 1 autoimmune polyglandular syndrome (APS-1), has a unique pathogenic mechanism owing to mutations in the autoimmune regulator (AIRE) gene, which results in the loss of central tolerance-a process by which developing T cells with potential reactivity for self-antigens are eliminated during early differentiation in the thymus. Patients with IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) syndrome harbor mutations in the forkhead box P3 (FOXP3) gene in regulatory T cells, which leads to severe autoimmunity and immune deficiency. Although both of these disorders are rare, their well-defined mechanisms of disease provide a basis for the understanding of the more common condition, APS-2. In this syndrome, alleles of human leukocyte antigens (HLAs) determine the targeting of specific tissues by autoreactive T cells, which leads to organ-specific autoimmunity as a result of this loss of tolerance. Non-HLA genes also contribute to autoimmunity in APS-2 and, depending on the polymorphism, potentially predispose to a loss of tolerance or influence which organ is specifically targeted. 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.
Authors:
Aaron W Michels; Peter A Gottlieb
Publication Detail:
Type:  Journal Article; Review     Date:  2010-03-23
Journal Detail:
Title:  Nature reviews. Endocrinology     Volume:  6     ISSN:  1759-5037     ISO Abbreviation:  Nat Rev Endocrinol     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-23     Completed Date:  2010-07-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101500078     Medline TA:  Nat Rev Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  270-7     Citation Subset:  IM    
Affiliation:
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 1775 Aurora Court, MS B140, PO Box 6511, Aurora, CO 80045, USA.
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MeSH Terms
Descriptor/Qualifier:
HLA-DR Antigens / genetics
Humans
Mutation
Polyendocrinopathies, Autoimmune / etiology*,  genetics,  therapy
Chemical
Reg. No./Substance:
0/HLA-DR Antigens

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