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Protein discovery sheds light on autoimmune diseases

The immune system is made up of a collection of mechanisms that protect our bodies from disease and infection. But if you have an autoimmune disease, your own immune system attacks itself by mistake. Many parts of the body can be affected by these diseases, including nerves, muscles, and the endocrine and digestive systems. Autoimmune diseases are the third leading cause of morbidity and mortality in the industrialised world and are only surpassed by cancer and heart disease. Now scientists working on an EU-funded project have identified a protein, which they say will lead to new ways of understanding and treating these autoimmune diseases.


The research will lead to new ways of understanding other autoimmune diseases © Shutterstock
The research will lead to new ways of understanding other autoimmune diseases
© Shutterstock

The three-year EurAPS project is funded under the ‘Life Sciences, genomics and biotechnology for health’ thematic area of the Sixth Framework Programme (FP6). Bringing together 16 partners from across Europe, as well as Australia and Hong Kong, the project studied a rare genetic disorder of early childhood called Autoimmune polyendocrine syndrome type I (APS-1). The findings are published in The New England Journal of Medicine.

APS-1 is a hereditary disease caused by mutations in a single gene called autoimmune regulator (AIRE). The mutation causes the immune system to produce auto-antibodies, which are then directed against one or more of the body’s proteins. APS-1 patients can have a wide range of symptoms. These symptoms include hypocalcemia from the destruction of the parathyroid glands and Addison’s disease from the destruction of the adrenal glands. In addition, those with the disease can also develop mucosal and skin infections with candida yeasts.

The researchers in the EurAPS project have now identified one of the proteins that comes under attack by the disease. Dubbed NALP5, this protein is the target for the immune system’s attacks on the parathyroid glands. The parathyroid glands are small endocrine glands in the neck, usually located behind the thyroid gland. They produce parathyroid hormone, which helps raise the concentration of calcium in the blood. The glands maintain the body's calcium level within a very narrow range, so that the nervous and muscular systems can function properly. When the blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated to release the hormone into the blood.

In patients with APS-1, the parathyroid glands can be knocked out at a very young age. This can lead to severe cramp attacks caused by the calcium imbalance, which are often hard to treat using regular treatment. If the disease is not discovered it can possibly lead to death. This new discovery is expected to allow an early diagnosis of the condition, so that young sufferers can receive the proper treatment.

The fact that the protein NALP5 was found in the parathyroid glands is expected to provide scientists with a more complete understanding of the function of these glands. In addition, the latest discovery increases the possibility of developing drugs and methods of treatment for those diseases which produce a calcium imbalance, for example osteoporosis.

The fact that the protein functions as a target for the immune cells in humans, but also in animal models with the same genetic defect, is good news for further research into the disease. ‘This means now, for the first time, in an experimental situation we will be able to compare the immune defense with exactly the same target protein in humans and in an animal model,' says Mohammad Ali Mohammadi at the Department of Medical Sciences, Uppsala University, who made the discovery.