APECED - Patients develop mucocutaneous candidiasis and endocrinopathies. Hypoparathyroidism and adrenocortical failure (Addison disease) are the most common endocrine manifestations. Less common features include ovarian failure, type I diabetes, and hypothyroidism.
APECED is caused by mutations in the gene for AIRE. AIRE is prominently expressed in medullary thymic epithelial cells. In the thymus, AIRE induces ectopic expression of self-antigens that are otherwise restricted to peripheral tissues. This allows for negative selection of self-reactive T cells and induction of central tolerance. Lack of AIRE expression allows for autoreactive T cells to escape thymic negative selection these cells cause multi-organ autoimmunity in the periphery.