Autoimmune Addison's disease as part of the autoimmune polyglandular syndrome type 1: historical overview and current evidences

The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants in the autoimmune regulator (AIRE) gene,located on human chromosome region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immunologicself-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in initiation and post-initiationevents of tissue-specific antigen-encoding gene transcription. Once synthesized, tissue-specific antigens are presented to, andcause deletion of, the self-reactive thymocyte clones. The clinical picture of APS1 relies on the triad idiopathic hypoparathyroidism(HPT), chronic mucocutaneous candidiasis and autoimmune primary adrenocortical insufficiency, usually referred to as autoimmuneAddison’s disease (AAD). Although HPT is in most cases the first endocrine component of APS1, the immunological, biochemical andclinical features of inherent AAD have received the best characterization. Here a review of the studies on APS1-associated AAD isoffered, from the initial case reports up to the most recent scientific acquisitions.