Elsevier

Autoimmunity Reviews

Volume 13, Issue 2, February 2014, Pages 85-89
Autoimmunity Reviews

Review
Autoimmune polyendocrine syndromes

https://doi.org/10.1016/j.autrev.2013.07.006Get rights and content

Highlights

  • The major autoimmune polyendocrine syndromes have a strong genetic component.

  • The discovery of the polyendocrine syndromes offered the possibility to understand autoimmune disorders.

  • Both major autoimmune polyendocrine syndromes have Addison’s disease as a prominent component.

  • Almost 40–50% of subjects with Addison’s disease will develop an associated endocrinopathy.

Abstract

Autoimmune polyendocrine syndromes (APS), also called polyglandular autoimmune syndromes (PGAS), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected.

The two major autoimmune polyendocrine syndromes, (type1–type2/APS-1 and APS-2), both have Addison's disease as a prominent component. Further autoimmune polyendocrine syndromes include APS3 and APS4.

The major autoimmune polyendocrine syndromes have a strong genetic component with the type 2 syndrome occurring in multiple generations and the type I syndrome in siblings.

It is well recognized that more than 20 years may elapse between the onset on one endocrinopathy and the diagnosis of the next, for example, almost 40–50% of subjects with Addison's disease will develop an associated endocrinopathy.

The discovery of the polyendocrine autoimmune syndromes offered the possibility to understand autoimmune disorders with particular interest for type 1A diabetes and the neuroendocrine immunology (NEI) is further contributing to understand the links.

Introduction

The term autoimmune polyendocrine syndromes (APS) comprise several and different conditions in which, however, not all patients necessarily have multiple endocrine disorders, and many have nonendocrine autoimmune diseases [1]. Interestingly, it is likely that the involved tissues and organs do not share any specific molecule but rather have different molecules that may more or less likely act as targets when the immune system fails to maintain self-tolerance to a variety of molecules.

The two major autoimmune polyendocrine syndromes, (autoimmune polyendocrine syndromes type1–type2/APS-1 and APS-2), both have Addison's disease as a prominent component, but exist also APS-3 and APS-4.

The major autoimmune polyendocrine syndromes have a strong genetic component with the type 2 syndrome occurring in multiple generations and the type I syndrome in siblings [2].

In addition, patients with APS-1 and APS-2 develop multiple diseases over time and approximately one out of seven relatives of them have an undiagnosed autoimmune disorder (most often hypothyroidism for the type 2 syndrome) [3].

For practical reasons the major pathological conditions associated with both APS-1 and APS-2 are listed in Table 1.

Section snippets

Pathogenetic factors

The APS-1 syndrome is almost always inherited in an autosomal recessive manner linked to mutation of the AIRE gene (AIRE: Autoimmune Regulator gene) on chromosome 21 [4], [5].

In autoimmune disorders including Addison's disease, patients without the APS-1 syndrome, do not show AIRE mutations suggesting that the gene alterations are not involved in these more common diseases.

In contrast, there is evidence that in rare diseases with abnormal T cell development (i.e. T-B-SCID or Omenn syndrome)

Pathogenetic factors

Differently from APS-1, genetic abnormalities underlie disease susceptibility for autoimmune polyendocrine syndrome type 2 (APS-2) and consist primarily of alleles of genes within the major histocompatibility complex [21]. The primary association of APS-2, similar to many autoimmune conditions appears to be with class II HLA alleles (immune response genes) and in particular with DQ2 and DQ8.

Therefore, APS-2 is has been found strongly associated with human leukocyte (HLA) haplotypes with DR3/DQ2

Conclusions

The discovery of the polyendocrine autoimmune syndromes offered the possibility to understand autoimmune disorders with particular interest for type 1A diabetes [52]. As matter of fact the early evidence that type 1A diabetes should be considered as an autoimmune disorder came from its association with spontaneous Addison's disease [53]. On the other side, the first demonstration of cytoplasmic islet cell autoantibodies occurred in patients with polyendocrine autoimmunity [54].

Moreover, the

Take-home messages

  • Autoimmune polyendocrine syndromes (APS—types 1/2/3/4) include several and different conditions in which, however, not all patients necessarily have multiple endocrine disorders, and many have nonendocrine autoimmune diseases.

  • The most frequent pathological conditions related to the APS-1 autoimmune polyendocrine syndrome include Addison's disease, hypoparathyroidism and mucocutaneous candidiasis.

  • APS-2 is the most common autoimmune polyendocrine syndrome and includes Addison's disease, Graves'

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