Autoimmune polyglandular syndrome type 1, also called APS type 1, or autoimmune polyendocrinopathy-candidiasis-ectodermal
dystrophy, also called APECED, is a rare, genetically inherited condition.
Autoimmune means that the body’s immune system begins to attack its own tissues, and
polyglandular means that multiple hormone-producing organs are affected.
Normally, your body should only react to things that are foreign or not-self.
This is maintained by a process called immune tolerance where only non-self-reactive B-cells
and T-cells, are allowed to mature, whereas self-reactive ones aren’t.
For T-cells, this process takes place in the thymus, where a gene called AIRE, or autoimmune
regulator, is expressed by thymic medullary epithelial cells.
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.
These hormones normally help to maintain blood pressure among many bodily processes and their
loss can be life-threatening.
In addition, chronic mucocutaneous candidiasis is an infection with the yeast Candida that
affects the skin and nails, as well as mucous membranes, like the mouth, esophagus, and
genital mucosa.
There’s also ectodermal dystrophy which leads to skin abnormalities like vitiligo
which causes areas of hypopigmentation, nails, corneas, reduced dental enamel, and alopecia
which is where there’s hair follicle destruction causing bald spots.
Finally, some non-endocrine organs like the liver, intestine, lungs, kidney, salivary
glands, and spleen can get inflamed as well.
Recognizing the clinical pattern early is particularly important in terms of making
a diagnosis and starting treatment early.
Diagnosis of APS type 1 is based on the presence of at least two of the three characteristic
manifestations, namely, chronic mucocutaneous candidiasis, hypoparathyroidism, and primary
adrenal insufficiency.
It also includes DNA testing to look for mutations in the AIRE gene and lab tests for autoantibodies
toward interferons, which are common in this condition.
Treatment depends on treating the manifestations of the condition that are present in each
person.
This can include hormone-replacement therapy, immunosuppressive medications in those with
non-endocrine organ damage, and calcium and vitamin D supplementation in those with hypoparathyroidism.
All right, as a quick recap...APS type 1 or APECED is a rare genetically inherited condition
caused by mutations in the autoimmune regulator, or AIRE, gene that results in a defect in
the development of immune tolerance.
Signs and symptoms include the malfunction of multiple glands such as the parathyroid
and adrenal glands, chronic mucocutaneous candidiasis, and ectodermal dystrophy and
autoimmune damage to non-endocrine organs.
In individuals that are thought to have the disease, the diagnosis includes the clinical
detection of these manifestations along with DNA testing and blood tests to look for interferon-targeting
autoantibodies.
Treatment includes hormone-replacement therapy, immunosuppressive medications in those with
end-organ damage, and calcium and vitamin D supplementation in those with hypoparathyroidism.