Genetic Dissection of Autoimmune Polyendocrine Syndrome Type 2

Abstract

Autoimmune diseases constitute a heterogeneous group of disorders characterized by the loss of immune tolerance to self-antigens. Despite their distinct clinical picture, there is growing evidence that common molecular mechanisms may contribute to the whole spectrum of autoimmune diseases. This theory is strongly supported by the existence of the autoimmune polyendocrine syndromes (APS). Thus, the clinical diagnosis of APS1 is made in an individual who presents with at least two out of three cardinal symptoms, namely autoimmune Addison's disease, autoimmune hypoparathyroidism, and mucocutaneous candidiasis. APS1 is a rare autosomal recessive syndrome caused by mutations in the autoimmune regulator (AIRE) gene. APS2, which occurs at a much higher frequency, is classically defined as the coexistence of autoimmune Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes. In contrast to APS1, the precise modes of inheritance and the genetic causes underlying APS2 remain unknown. Identification of genetic factors predisposing to this syndrome may contribute to our understanding of common mechanisms involved in autoimmunity.

The epidemiology of Graves' disease: Evidence of a genetic and an environmental contribution

“…Addison's disease showed a high association of 2.52, which could suggest an etiological contribution by autoimmune polyendocrine syndrome, as also type 1 diabetes mellitus (3.37 from parent, 2.14 from sibling), Hashimoto/hypothyroidism and pernicious anemia were associated [7,11,38]. Other disease with strong association with Graves' disease were discoid lupus erythematosus (sibling risk 6.03, higher than for concordant Graves' disease), localized scleroderma (sibling risk 6.62), polymyositis/dermatomyositis (2.46) and myasthenia gravis (2.04).…”

Autoimmune Hepatitis as a Part of Polyglandular Autoimmune Syndrome Type II: Case Report and Literature Review

“…PAS type 1 is well defined and caused by a mutation in the autoimmune regulator gene AIRE [3][4][5]. Addison's disease occurring in PAS type 1 is associated with chronic mucocutaneous candidiasis and/or acquired hypoparathyroidism [6].…”

“…As there has already been a well-defined type of AIH associated with PAS type I, these investigators conclude that this patient could have an alternative form of autoimmune hepatitis which occurs with PAS type II and has a unique genetic linkage [5,14].…”

Aire's partnerships: An answer for many questions and new questions in search of answers

“…While the relevance of Aire mutations in Type 1 APS is established and constitutes a model for the loss of Aire function, the elucidation of role of Aire in Type 2 APS, which includes subpopulations with T1D, has proven elusive. There are gender‐associated changes in incidence of type 1 diabetes in type 2 APS, where prevalence is higher in females (10, 11). Gender‐related differences in methylation have been described in health (12) and in diseases such as cancer (13) and diabetes (14, 15).…”