Systemic scleroderma (systemic scleroderma) - IRF5 and STAT4 Genes

Systemic scleroderma, also known as systemic sclerosis or scleroderma progressive familial, is an autoimmune disease that affects the skin and internal organs, characterized by the accumulation of scar tissue in the skin and other organs. Alteration called systemic sclerosis because fibrosis can affect other organs besides the skin. Fibrosis is due to excess production of collagen, which strengthens and supports the connective tissues throughout the body.

Usually the signs and symptoms of the disease begin with episodes of Raynaud's phenomenon, which may occur weeks or years before fibrosis. In Raynaud's phenomenon, the fingers of the affected people turn white or blue in response to cold temperatures or other stresses. This effect occurs because of problems with small vessels that carry blood to the extremities. Another early sign of systemic scleroderma are swollen or swollen hands before thickening and hardening of the skin due to fibrosis. Generally, thickening of the skin is initially produced in the fingers and can also affect the hands and face. In addition, these individuals have ulcers on the fingers, calcinosis and telangiectasias. Fibrosis can also affect internal organs and can lead to deficiency or failure of the affected organs. Most often, the affected organs are the esophagus, heart, lungs and kidneys. The internal organ can manifest through heartburn (heartburn), dysphagia, hypertension, kidney disease, respiratory distress, diarrhea or intestinal pseudo - obstruction.

They described three types of systemic scleroderma, which vary depending on the tissues affected. In one systemic scleroderma, known as limited cutaneous systemic scleroderma, fibrosis usually affects only the hands, arms , and face. This guy used to be known as CREST syndrome, named after the common characteristics of alteration: calcinosis, Raynaud's phenomenon, esophageal motility dysfunction, Sclerodactyly and telangiectasia. In other systemic scleroderma, systemic scleroderma skin known as diffuse fibrosis affects large areas of the skin, including the torso, arms and legs and often internal organs. In diffuse cutaneous systemic scleroderma, the disease gets worse quickly and organ damage occurs earlier than in other types of disease. In the third type of systemic scleroderma, systemic sclerosis called sine scleroderma, fibrosis affects one or more internal organs, but not to the skin.

Approximately 15 and 25% of people with characteristics of systemic scleroderma manifest signs and symptoms of other disease affecting connective tissue, such as polymyositis, dermatomyositis, rheumatoid arthritis, Sjogren's syndrome or lupus erythematosus systemic. The combination of systemic scleroderma with other abnormalities of connective tissue known as scleroderma overlap syndrome.

They have identified several genes that may influence the risk of developing systemic scleroderma. Genes associated with this process most often belong to a gene family known human leukocyte antigen complex (HLA). The HLA complex helps the immune system distinguish the body's own proteins own foreign agents such as viruses and bacteria proteins. Each HLA gene has many different normal variations, allowing the immune system reacts to each individual a wide range of foreign proteins. Specific normal variations of various HLA genes appear to affect the risk of developing systemic scleroderma. Normal variations in other related body 's immune function, such as IRF5 and STAT4, genes are also associated with increased risk of systemic scleroderma. Specifically, variations in the IRF5 gene associated with diffuse cutaneous systemic scleroderma, and a variation in the gene is associated with STAT4 limited cutaneous systemic scleroderma. IRF5 and STAT4 the genes play a role in initiating an immune response when the body detects a pathogen.

IRF5 gene, located on the long arm of chromosome 7 (7q32), encodes a protein called interferon regulatory factor 5 (IRF5), which acts as a transcription factor. When a virus is detected in a cell, the gene encodes IRF5 IRF5 protein. The protein binds to specific DNA regions that regulate the activity of genes encoding interferons and other cytokines. Cytokines are proteins that help fight infection and inflammation by regulating the activity of immune system cells. In particular, interferons control the activity of genes that help block virus replication, and stimulate the activity of certain immune system cells known as natural killer cells (NK cells). Several mutations in the gene IRF5 been associated with increased risk of systemic scleroderma. Although it is known that the gene IRF5 stimulates the immune system in response to viral infections, it is not clear how genetic variations contribute to the increased risk of systemic scleroderma. It is likely that a combination of genetic and environmental factors may play a role in disease development.

STAT4 gene, located on the long arm of chromosome 2 (2q32.2-q32.3), encodes a protein that acts as a transcription factor. This protein is activated by cytokines, which are part of the inflammatory response to fight infection. When activated, the STAT4 protein increases the activity of genes that help T cells to mature into specialized T cells. These specialized T cells, called Th1 cells encoding specific cytokines and stimulate other immune to get rid of cell pathogens cells. It has identified a change in the STAT4 gene associated with increased risk of systemic scleroderma. Although it is known that the STAT4 gene stimulates the immune system in response to pathogens it is unclear how genetic variation contributes to the increased risk of systemic scleroderma. It is likely that a combination of genetic and environmental factors may play a role in disease development.

Most cases of systemic scleroderma are sporadic, meaning that occur in people with no history of disease in your family. However, some people with systemic scleroderma have close relatives with other autoimmune disorders. It has identified a small percentage of all cases of systemic scleroderma in families; however, the disease has no clear pattern of inheritance. It is likely that multiple genetic and environmental factors play a role in determining the risk of developing this condition.

Tests in IVAMI: in IVAMI perform detection of mutations associated with systemic scleroderma, by complete PCR amplification of exons IRF5 and STAT4 genes, 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).