Autoimmune Polyendocrinopathy, Candidiasis, and Ectodermal Dystrophy Syndrome
APECED is a rare autosomal recessive disorder, also known as autoimmune polyglandular syndrome (APS) type I. The incidence is high in certain isolated populations, for example, Finns, Iranian Jews, and Sardinians. Most patients with APECED present with chronic mucocutaneous candidiasis and endocrinopathies predominantly involving the parathyroid and adrenal glands, less frequently the thyroid and the pancreas. The syndrome is often associated with ectodermal manifestations such as dystrophic dental enamel and fingernails.138 APECED results from mutations in the AIRE gene. AIRE expression is limited to medullary thymic epithelial cells which express MHC class II and the costimulatory molecule CD80. These cells are endowed with the remarkable ability to “promiscuously” express a wide variety of tissue-restricted antigens derived from nearly all organs in the body.139 Expression of these organ specific proteins allows for the negative selection of autoreactive T cells or the generation of immunoregulatory FOXP3+ T cells in the thymus. A lack of AIRE function causes decreased expression of tissue restricted antigens in the thymus, resulting in the escape of autoreactive T-cell clones into the periphery.