AUTHOR=Perniola Roberto , Fierabracci Alessandra , Falorni Alberto 

TITLE=Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.606860

DOI=10.3389/fimmu.2021.606860

ISSN=1664-3224

ABSTRACT=<p>The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator (<italic>AIRE</italic>) gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Once synthesized, the self-antigens are presented to, and cause deletion of, the self-reactive thymocyte clones. The clinical diagnosis of APS1 is based on the classic triad idiopathic hypoparathyroidism (HPT)—chronic mucocutaneous candidiasis—autoimmune Addison's disease (AAD), though new criteria based on early non-endocrine manifestations have been proposed. HPT is in most cases the first endocrine component of the syndrome; however, APS1-associated AAD has received the most accurate biochemical, clinical, and immunological characterization. Here is a comprehensive review of the studies on APS1-associated AAD from initial case reports to the most recent scientific findings.</p>