Endocrine Abstracts

Autoimmune endocrine diseases such as type 1 diabetes and autoimmune adrenal insufficiency (Addison’s disease) are disorders that often aggregate in families. Despite being universally lethal before the 20th century, the predisposing genetic variants have remained in the population, probably conferring advantages even at the price of an enhanced risk of developing autoimmunity. With carefully phenotyped patients and geographically matched controls, strong signals can be obtained in genome wide associations studies (GWAS) even with small cohorts in rare diseases. In patients with autoimmune adrenal insufficiency positive for 21-hydroxylase autoantibodies genetic variants of MHC, BACH2 and AIRE have emerged as the most important risk genes.

Monogenic disorders such as Autoimmune Polyendocrine syndrome (APS-1) and Immune Dysregulation Polyendocrinopathy, Enteropathy, X-linked (IPEX) have proved invaluable for our understanding of the events eventually leading to endocrine autoimmunity. These rare syndromes have helped us identify the genes AIRE and FOXP3, critical for important tolerance mechanisms. They also represent good examples of how research on rare disorders translate into novel diagnostic tools and better understanding of more common autoimmune disorders, and at the same time improve clinical care practices for patients with APS-1 and IPEX.