Endocrine Medicine
Reseach project

Autoimmune Polyendocrine Syndrome type 1 (APS 1)

Main content

The T cells are central in the adaptive part of our immune system. The T cells carry surface molecules, receptors, which recognize pathogens that enter our body. It is crucial that T cells are able to separate between self and non-self, and only enter an immune response towards non-self; this is termed immunological tolerance. Immunological tolerance is established during the T cells maturation in the thymus. The thymus is an organ located above the heart, where the T cells learn the difference between self and non-self.

The autoimmune regulator (AIRE) is a transcription factor that is primarily expressed in the thymus. Here, AIRE regulates the expression of multiple proteins that are usually seen in distant organs to display to the developing T cells. For examples, AIRE regulates the expression of insulin, and T cells that bear reseptors that regcognise insulin will be deleted. This was, only T cells bearing receptors that do not recognize self will be released from the thymus (Figure 1A). Without AIRE, insulin is not expressed and the T cells that recognise insulin is released into circulation where they will target pancreatic cells (Figure 1B).

Aire funksjon

Figure 1. In cases of normal central immune tolerance, the autoimmune regulator (Aire) that is expressed in medullary thymic epithelial cells (mTEC) promotes expression of tissue-specific antigens, which are displayed on the surface. Autoreactive T cells With affinity for self-proteins either die by apoptosis or become forkhead box P3 (FoxP3)–expressing regulatory T cells (Tregs). When Aire is lacking (bottom), the tissue-specific antigens are not displayed on the mTEC surface and autoreactive T cells escape to the general circulation and peripheral lymphoid organs, where they can cause autoimmune reactions and APS-1. A lack of Tregs also contributes to autoimmunity

New England Journal of Medicine

When AIRE is non-functional due to mutations in the gene, you develop the disease autoimmune polyendocrine syndrome type I (APS-1). This is a serious disease which might lead to a preliminary death without proper treatment. APS-1 manifests with chronic candidiasis infections usually within the first year of life, and then the development of the autoimmune diseases Addison’s disease and hypoparathyroidism. Two of these three manifestations are the basis of a clinical diagnosis, but the patients often develop a range of different autoimmune disease (Figure 2).  This is a unique autoimmune disease, where mutations in one gene is the underlying cause. Studies of AIRE and APS-1 has given us invaluable information about the establishment of immunological tolerance, and how this is broken in autoimmune diseases. Our national register Register for organ-spesifikke autoimmune sykdommer (ROAS) is one of the world’s largest collection of biological samples from patients with APS-1.

Symptomer ved APS-1

Shown are the main manifestations of autoimmune polyendocrine syndrome 1 (APS-1) and other similar polyendocrine syndromes

New England Journal of Medicine