Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a model disease to study molecular aspects of endocrine autoimmunity

Many of the organ-specific autoimmune diseases affect endocrine organs. This is due to the fact that the organ-specific autoantigens are often hormones or enzymes specifically engaged in the synthetic pathways resulting in hormone production. Autoimmune endocrine diseases include type 1 diabetes, hypo- and hyperthyroidism, Addison's disease, hypoparathyroidism, and gonadal failure. These diseases may occur as a solitary immunological abnormality but often coincide as polyendocrine autoimmune diseases, indicating a common aetiology in the pathogenesis. Autoimmune endocrine diseases have complex genetic predispositions and they are closely associated to certain HLA haplotypes. In addition to HLA, other genes are known to regulate the disposition to autoimmunity. Only a few autoimmune diseases with a monogenic background are known. An example is a syndrome regulated by a single gene, namely APECED, an acronym for autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, also known as autoimmune polyendocrinopathy syndrome type 1 (APS1). In this autosomal recessive disease, mutations in the AIRE (autoimmune regulator) gene cause organ-specific autoimmune destruction of several, mostly endocrine, tissues. This article reviews current knowledge of APECED and the AIRE gene behind this syndrome.