autoimmune polyendocrine syndromes

Definition : The autoimmune polyglandular syndromes is a group of syndromes comprising a combination of endocrine and nonendocrine autoimmune diseases.

They differ in their component diseases and in the immunologic features of their pathogenesis.

One of the three main syndromes, type 1 autoimmune polyglandular syndrome (APS1), 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 APS2 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 APS1, APS2 and IPEX syndrome, with an emphasis on the mechanisms of autoimmunity and presents currently available therapies to treat their underlying autoimmune disorders.

Types

 APECED or autoimmune polyendocrinopathy syndrome type 1 (APS1)
 autoimmune polyendocrinopathy syndrome type 2 (APS2)
 IPEX syndrome

Synopsis

 autoimmune hypogonadism
 autoimmune adrenal insufficiency

References

 Autoimmune polyglandular syndromes. Michels AW, Gottlieb PA. Nat Rev Endocrinol. 2010 May;6(5):270-7. PMID: 20309000

 Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med. 2004 May 13;350(20):2068-79. PMID: 15141045

 Dotta F, Vendrame F. Neonatal syndromes of polyendocrinopathy. Endocrinol Metab Clin North Am. 2002 Jun;31(2):283-93 PMID: 12092451