Autoimmune Addison's disease (AAD) results from the immune-mediated destruction of adrenocortical cells. AAD is a major component of the autoimmune polyendocrine syndromes type 1 (APS 1) and type 2. The adrenal autoimmune process is made evident by the apperance of circulating autoantibodies against the steroidogenic enzyme 21-hydroxylase. Detection of 21-hydroxylase in patients with endocrine autoimmune diseases enables the identification of subjects with preclinical AAD. An impaired response to a corticotrophin stimulation test marks the irreversible stage of preclinical AAD and predicts progression towards clinical AAD in over 80% of cases. APS 1 is caused by mutations of the autoimmune regulator (AIRE) gene, which encodes an activator of transcription, Aire, that induces the expression of autoantigens in thymic medullary epithelial cells and promotes immunological tolerance. Isolated and APS 2-related AAD is an autoimmune disease with evidence for complex genetic susceptibility caused by T-cell-mediated destruction of adrenocortical cells, with a major contribution of HLA genes. The target cells in the adrenal cortex participate in the immune reaction by releasing chemokines, such as CXCL-10, that attract Th1 cells.
Keywords: 21-hydroxylase; Addison’s disease; Aire; CXCL-10; HLA; T cell; autoantibodies; primary ovarian insufficiency.