6 Autoimmune polyglandular syndromes

Autoimmune polyglandular syndrome type 1 (APS1) is characterized by a variable combination of disease components: (1) mucocutaneous candidiasis; (2) autoimmune tissue destruction; (3) ectodermal dystrophy. The disease is caused by mutations in a single gene called APECED (autoimmune polyendocrinopathy-candidiasis-ectodermaldystrophy) or AIRE (autoimmune regulator) coding for a putative transcription factor featuring two zinc-finger (PHD-finger) motifs. APS1 shows a penetrance of 100%, lack of female preponderance and lack of association with HLA-DR. Typically, onset of APS1 occurs in childhood and multiple autoimmune manifestations evolve throughout lifetime. Organ-specific autoantibodies associated with hypoparathyroidism, adrenal and gonadal failures, IDDM, hepatitis and vitiligo are discussed, and autoantibody patterns in APS1 patients are compared with autoantibodies in APS type 2 (APS2). APS2 is characterized by adult onset adrenal failure associated with IDDM and/or hyperthyroidism. APS2 is believed to be polygenic, characterized by dominant inheritance and association with HLA DR3.