Autoimmune Polyglandular Syndrome Type 1

Abstract

Autoimmune polyglandular syndrome type 1 (APS1) is a monogenic autoimmune disease with organ-specific autoimmune destruction of several endocrine tissues. Most common disorders of the syndrome are chronic mucocutaneous candidiasis, hypoparathyoidism and Addison’s disease but the clinical spectrum may vary. The disease is caused by the mutations in autoimmune regulator (AIRE) gene. More than 50 mutations have been described, which are spread over the AIRE gene with two major mutation hotspots, R257X and 967-979del13bp. AIRE protein has several motifs supporting its role in transcriptional control and is highly expressed in thymic medullary epithelial cells. Analysis of AIRE deficient mice have demonstrated its role in transcriptional regulation of tissue specific antigens in medullary thymic epithelial cells, and suggested that AIRE is critical protien responsible for the maintenance of central tolerance. In agreement with mouse model, patients with APS1 have autoantibodies to multiple self-proteins. The data on cell-mediated immune responses and the reason for chronic candidiasis are still elusive. The identification of AIRE mutations and a recent finding of high titre autoantibodies to type 1 interferons should facilitate diagnosis of APS1.