Genetic dissection of autoimmune polyendocrine syndrome type 2: common origin of a spectrum of phenotypes

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.