Content Reviewers:Rishi Desai, MD, MPH
Normally, your body should only react to things that are foreign or not-self.
When T-cells are developing, this gene leads to the production of thousands of the body’s proteins, and this serves as a test to see whether the T-cells react to self proteins.
If one does, that T-cell either undergoes apoptosis and dies, or it becomes a regulatory T-cell, or T-reg, that helps to eliminate other immune cells that react to self antigens.
In APS type 1, there’s a genetic mutation in AIRE that’s usually inherited in an autosomal recessive fashion.
This means that the thymic medullary epithelial cells lose the ability to display the body’s different self-proteins.
Since they can no longer test whether T-cells are self-reactive or not, the process of immune tolerance does not occur normally, and self-reactive T-cells are allowed to live.
Regulatory T-cells are no longer produced normally either, so the body loses a second mechanism for destroying autoimmune cells.
This allows for the production of antibodies and lymphocytes that target normal tissues of the body. It is still unclear why, but certain glandular tissues, including the adrenal glands and parathyroid glands, are particularly targeted.
There are multiple characteristic signs and symptoms of APS type 1.
One of them is polyendocrine malfunction resulting in hypoparathyroidism, characterized by low calcium and elevated phosphorus in the blood that can cause muscle cramping and seizures, and primary adrenal insufficiency, also called Addison’s disease, which can reduce cortisol and aldosterone levels.