Addison autoimmune, disease ..., (Autoimmune Addison disease) - Genes CIITA , CTLA4 , CYP27B1 , HLA-DQA1 , HLA-DQB1 , HLA-DRB1 , MICA , NLRP1 and PTPN22

Autoimmune Addison's disease is an autoimmune process that affects the function of the adrenal glands. As a result, production of various hormones is interrupted, which affects many body systems.

Signs and symptoms of autoimmune Addison's disease can begin at any time, but most often begin between 30 and 50 years and generally include extreme fatigue, nausea, decreased appetite, weight loss, hypotension and muscle cramps. A characteristic feature of autoimmune Addison's disease are areas of skin hyperpigmentation, especially in regions of frequent friction, such as the armpits, elbows, knuckles and palms. Lips and the inner lining of the mouth may also be unusually dark. Other signs and symptoms of autoimmune Addison's disease include hypoglycemia, hyponatremia, hypercalcemia, anemia, lymphocytosis and eosinophilia. Autoimmune Addison's disease can result in a potentially fatal adrenal crisis, characterized by vomiting, abdominal pain, back spasms or legs and severe hypotension that can lead to shock. Often adrenal crisis is triggered by a stressor, such as surgery, trauma or infection. In addition, individuals with autoimmune Addison 's disease or their families may suffer autoimmune thyroid disease or type 1 diabetes.

The cause of autoimmune Addison's disease is complex and not fully understood. It is believed that in addition to alterations in several genes, that a combination of environmental factors can increase the risk of developing the process. Genes that have been associated with autoimmune Addison 's disease participate in the body 's immune response. Genes associated most often belong to a family of genes called the human leukocyte antigen complex (HLA). The HLA complex helps the immune system to distinguish self proteins body of proteins encoded by invading agents such as viruses and bacteria. Each HLA gene has many different normal variations, allowing the immune system reacts to each individual a wide range of foreign proteins. The factor most known risk for autoimmune Addison's disease is a variant of the HLA-DRB1 gene , called HLA-DRB1 * 04: 04. This and other variants of HLA gene associated with the disease, probably contribute to an inappropriate immune response resulting in development of the disease, although the mechanism is unknown.

The immune system normally responds only to the proteins encoded by foreign invaders, and not facing the body's own proteins. However, autoimmune Addison's disease, an immune response by a normal protein is induced adrenal gland, usually a protein called 21-hydroxylase. This protein plays a key role in the production of certain hormones in the adrenal glands. The immune attack extended triggered by the 21-hydroxylase damages the adrenal glands, inhibiting the production of hormones. Adrenal insufficiency interrupted several normal functions in the body, leading to hypoglycemia, hyponatremia, hypotension, muscle cramps, skin hyperpigmentation and other features of autoimmune Addison's disease.

Rarely, Addison's disease is not caused by an autoimmune reaction. Other possible causes include infections that damage the adrenal glands, such as tuberculosis or tumors in the adrenal glands. Addison's disease can also be one of several features of other genetic diseases, including X - linked adrenoleukodystrophy and autoimmune polyglandular syndrome type 1, which are due to mutations in other genes.

Changes have been identified in several genes that increase the risk of developing this disease, which include:

  • CIITA (class II major histocompatibility complex transactivator), 16p13.13.
  • CTLA4 (cytotoxic T-lymphocyte associated protein 4), 2q33.2.
  • CYP27B1 (cytochrome P450 family 27 subfamily B member 1), 12q14.1.
  • HLA-DQA1 (major histocompatibility complex, class II, DQ alpha 1), 6p21.32.
  • HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1), 6p21.32.
  • HLA-DRB1 (major histocompatibility complex, class II, DR beta 1), 6p21.32.
  • MICA (MHC class I polypeptide-related sequence A), 6p21.33.
  • NLRP1 (NLR family pyrin domain containing 1), 17p13.2.
  • PTPN22 (Protein tyrosine phosphatase, non-receptor type 22), 1p13.2.

The pattern of inheritance of autoimmune Addison's disease is unknown, however, it is a process that is transmitted across generations.

Tests performed in IVAMI: in IVAMI perform the detection of mutations associated with Addison's disease Autoimmune by the complete PCR amplification of the exons of the gene CIITA , CTLA4 , CYP27B1 , HLA-DQA1 , HLA-DQB1 , HLA-DRB1 , MICA , NLRP1 and PTPN22 , respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).