Question

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2) Autoimmune polyendocrinopathy ectodermal dystrophy (APECED) is a combined autoimmune/immunodeficiency disorder triggered by defects in expression of the gene AIRE (for the autoimmune regulator). AIRE expression is believed to allow for the production of a ‘shadow self’ within the thymus, allowing for multiple tissue-specific antigens (e.g. insulin from the pancreas, or gonadotropin-releasing hormone from the hypothalamus) to be expressed at very low levels by thymic stromal cells. Thus, AIRE expression strongly correlates with the principle of ‘central tolerance’ whereby autoreactive T cells are deleted by negative self-selection in the thymus.

Read up on APECED, and pick two of the syndrome’s immunological problems. Explain or hypothesize how these defects arise from a failure of AIRE expression.  

(10 points, 5 points per condition)

Answer:

APECED or autoimmune polyendocrinopathy ectodermal dystrophy is an autoimmune disease that is caused by a defect in the AIRE protein. Under the normal functioning of the body, many T cells are produced which may react negatively with the antigens of the body itself, thus disrupting many important and core functions required for the normal functioning of the body (Gregory & Lionakis, 2019). The AIRE protein functions to identify and subdue these antibodies, and in case of any defect of AIRE, these T cells subsequently produced will cause autoimmune diseases.

Usually, in case the AIRE protein is malfunctioning, the effects in the form of autoimmune diseases are usually visible by early childhood. There are several diseases pertaining to this condition, three of the main ones are described as follows:

1. Chronic mucocutaneous candidiasis
2. Hypo para thyroidism
3. Adrenal gland insufficiency

At least two of the three aforementioned conditions must be present in a person at a given moment, who is suffering from some autoimmune disease.

Chronic mucocutaneous candidiasis

This is the first problem that usually appears when you happen to suffer from APECED. Its symptoms include infections on nails, mouth and basically anywhere else with a mucosal lining. These moist areas are usually attacked by the fungi of the candida family (e.g.: Candida Albicans) and these are called yeast infections that are more than often of severe and chronic nature. The person suffering often suffers from an infection in the oral cavity, esophagus and in cases of women, the vaginal cavity as well.

Hypo para thyroidism

The parathyroid glands are secreting hormones, mainly the parathyroid hormone that regulates calcium and phosphorus. The deficiency caused will lead to a tingling sensation in lips, muscle cramps, weakness, and fatigue as well. the severe cases will see muscular spasms and respiratory collapse.

Adrenal gland insufficiency

The adrenal glands are usually heavily effected and therefore will case several metabolic deficiencies in the body. Loss of appetite, short stature, yellowing of the skin, weight loss and slow blood pressure as well.

The hypothesis of how AIRE dysfunctionality occurs and its relation to the conditions above:

1. The first and foremost reason for the unavailability of AIRE, to help the normal functioning of the immune system is obviously a mutation in its genetic background. AIRE has its genes at position 22.3 on the long (q) arm of chromosome 21 with the exact co-ordinates of Cytogenetic Location: 21q22.3. an aberration in base pairs will definitely cause malfunctioning of sorts (reference, 2020).

Autoimmune polyglandular failure type 1 (APS1), is a recessive form of hypoparathyroidism which in turn is unvaryingly caused by Mutations of the autoimmune regulator gene (AIRE) gene this is also called autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which we have discussed in detail before (Ergun-Longmire & Maclaren, 2016).

Answer 1

APECED or autoimmune polyendocrinopathy ectodermal dystrophy is an autoimmune disease that is caused by a defect in the AIRE protein. Under the normal functioning of the body, many T cells are produced which may react negatively with the antigens of the body itself, thus disrupting many important and core functions required for the normal functioning of the body (Gregory & Lionakis, 2019). The AIRE protein functions to identify and subdue these antibodies, and in case of any defect of AIRE, these T cells subsequently produced will cause autoimmune diseases.

Usually, in case the AIRE protein is malfunctioning, the effects in the form of autoimmune diseases are usually visible by early childhood. There are several diseases pertaining to this condition, three of the main ones are described as follows:

1. Chronic mucocutaneous candidiasis
2. Hypoparathyroidism
3. Adrenal gland insufficiency

At least two of the three aforementioned conditions must be present in a person at a given moment, who is suffering from some autoimmune disease.

Chronic mucocutaneous candidiasis

This is the first problem that usually appears when you happen to suffer from APECED. Its symptoms include infections on nails, mouth and basically anywhere else with a mucosal lining. These moist areas are usually attacked by the fungi of the candida family (e.g.: Candida Albicans) and these are called yeast infections that are more than often of severe and chronic nature. The person suffering often suffers from an infection in the oral cavity, esophagus and in cases of women, the vaginal cavity as well.

Hypoparathyroidism

The parathyroid glands are secreting hormones, mainly the parathyroid hormone that regulates calcium and phosphorus. This hormone increase serum calcium levels by activating osteoclasts which causes bone resorption.The deficiency caused will lead to a tingling sensation in lips, muscle cramps, weakness, and fatigue as well. The severe cases will see muscular spasms and respiratory collapse.

Adrenal gland insufficiency

The adrenal glands are usually heavily effected and therefore will case several metabolic deficiencies in the body. Loss of appetite, short stature, yellowing of the skin, weight loss and slow blood pressure as well.

The hypothesis of how AIRE dysfunctionality occurs and its relation to the conditions above:

1. The first and foremost reason for the unavailability of AIRE, to help the normal functioning of the immune system is obviously a mutation in its genetic background. AIRE has its genes at position 22.3 on the long (q) arm of chromosome 21 with the exact co-ordinates of Cytogenetic Location: 21q22.3. an aberration in base pairs will definitely cause malfunctioning of sorts (reference, 2020).

Autoimmune polyglandular failure type 1 (APS1), is a recessive form of hypoparathyroidism which in turn is unvaryingly caused by Mutations of the autoimmune regulator gene (AIRE) gene this is also called autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which we have discussed in detail before (Ergun-Longmire & Maclaren, 2016).