Gene AIRE – Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia

OMIM 240300

The AIRE gene provides instructions for making a protein called the autoimmune regulator. This protein is active primarily in the thymus, which is an organ located behind the breastbone that plays an important role in immune system function. The thymus prepares immune cells called T cells for their role in fighting infection; this process is called thymic education.

For a person to remain healthy, immune system cells such as T cells must be able to identify and destroy potentially harmful invaders (such as bacteria, fungi, and viruses) while sparing the body’s normal tissues. The autoimmune regulator protein plays an important role in this process by helping T cells distinguish the body’s own proteins from those of foreign invaders. When this system malfunctions, the immune system’s ability to distinguish between the body’s proteins and foreign invaders is impaired, and it may attack the body’s own tissues and organs. This abnormal reaction is called autoimmunity. In the thymus, the autoimmune regulator protein destroys T cells that otherwise would cause autoimmune damage.

More than 90 mutations in the AIRE gene have been identified in people with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). APECED is an inherited condition that affects many of the body’s organs. A major feature of this disorder is chronic mucocutaneous candidiasis (CMC), which is a tendency to develop infections of the skin, the nails, and the moist lining of body cavities (mucous membranes) caused by a type of fungus called Candida. Other common signs and symptoms of APECED involve dysfunction of the body’s network of hormone-producing glands (the endocrine system), as well as other organs and tissues.

The AIRE gene mutations that cause APECED lead to the production of an abnormally short, nonfunctional version of the autoimmune regulator protein or change single protein building blocks (amino acids) in critical regions of the protein. These mutations reduce or eliminate the function of the autoimmune regulator protein. Without enough of this protein function, the immune system’s ability to distinguish between the body’s proteins and foreign invaders is impaired, and immune cells may attack the body’s own organs, resulting in autoimmunity. This abnormal reaction leads to inflammation and can damage otherwise healthy cells and tissues. Autoimmune damage to the adrenal glands, parathyroid glands, and other organs underlies many of the major features of APECED.

(Source: Genetics Home Reference)