The Department of Biomedicine

BBB seminar: Eystein Husebye

Autoimmune polyendocrine syndrome type I – model disease of organ-specific autoimmunity

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Eystein Husebye
Section of Endocrinology, Institute of Medicine, University of Bergen

Autoimmune polyendocrine syndrome type I (APS-I) (OMIM 240300), also known as APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy), is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21. The disorder typically begins in early childhood and the patients gradually develop autoimmune destruction of different endocrine and non-endocrine tissues and, in addition, mucocutaneous candidiasis. The disease is characterized by autoantibodies against several, defined antigens, most often tissue-specific enzymes with important functions in the affected tissues and identical to those found in more common isolated autoimmune disorders such as type 1 diabetes mellitus and Addison's disease. However, tissue destruction is thought to be mediated by autoreactive T cells. APS-I is more prevalent in certain populations, such as among Finns (1:25000), Sardinians (1:14000) and Iranian Jews (1:9000).

The expression of AIRE in the thymus indicates a central function in the negative selection of T cells. It is thought that AIRE regulates the expression of tissue-specific proteins in the thymus, e.g. insulin and C-reactive peptide. This promiscuous expression seems to be necessary to remove autoreactive T cells against various self proteins. Lack of AIRE function leads to leakage of autoreactive cells into the circulation, which later have the potential to trigger an autoimmune disease process. APS I as a model disease, has proved to be instrumental in unravelling aspects of the pathogenesis of autoimmunity.

Host: Marit Bakke, Department of Biomedicine