Systemic lupus erythematosus (Systemic Lupus Erythematosus)
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that causes inflammation in the connective tissue, such as cartilage and the lining of blood vessels. Signs and symptoms of SLE vary between individuals affected and may involve many organ systems including the skin, joints, kidneys, lungs, central nervous system and the hematopoietic system.
In general, the first manifestations associated with SLE may be extreme fatigue, malaise, fever, loss of appetite and weight loss. Most affected individuals also have joint pain, which usually affects the same joints on both sides of the body as well as muscle pain and weakness. In addition, there are also frequent skin problems. A characteristic feature is a flat red rash across the cheeks and bridge of the nose, known as "butterfly rash" because of its shape. The rash, which usually does not cause pain or itching, usually appear or become more pronounced by exposure to sunlight. Other skin problems that may occur in SLE include calcinosis under the skin, petechiae and vasculitis. Petechiae are due to a deficiency of platelets that causes skin bleeding. Affected individuals may also have alopecia and ulcerations in the lining of the mouth, nose, or, less often, genitals.
About one third of people with SLE develop nephritis. Heart problems can also occur in SLE, including pericarditis, cardiac abnormalities and atherosclerosis valves. The inflammation characteristic of SLE can also damage the nervous system, and may lead to peripheral neuropathy, seizures and cognitive impairment. Anxiety and depression are also common in SLE. In general, the LES gradually worsens over time, and damage to major organs of the body can be potentially fatal.
This process may be induced by polymorphisms in many genes, and in most cases are thought to be involved multiple genetic factors. In rare cases, the LES is due to mutations in single genes. Most of the genes associated with SLE are involved in immune system function, and variations in these genes are likely to affect the orientation and control of the appropriate immune response. Sex hormones and a variety of environmental factors, including viral infections, diet, stress, exposure to chemicals and exposure to sunlight, is also believed to play a role in triggering this complex process. About 10 percent of cases of SLE is thought to be due to exposure to drugs, more than 80 drugs that could be implicated been identified.
In people with SLE, cells that have undergone apoptosis be damaged or no longer needed, not disposed of properly. However, the relationship of this loss of function to the cause of the features of SLE is unclear. It has been suggested that these dead cells can release substances that cause the immune system reacts inappropriately and attack the body's tissues, resulting in the signs and symptoms of SLE.
Some of the genes that have been associated with the development of systemic lupus erythematosus include BANK1 (B-cell scaffold protein With ankyrin repeats 1), C4A (complement component 4A (Rodgers blood group)), C4B (complement component 4B (Chido blood group )), C4B_2 (complement component 4B (Chido blood group), copy 2) CR2 (complement component 3d receptor 2), CRP (C-reactive protein, pentraxin-related), CTLA4 (cytotoxic T-lymphocyte associated protein 4), Dnase1 (deoxyribonuclease I), DNASE1L3 (Deoxyribonuclease I like 3), FCGR2B (Fc fragment of IgG IIb receptor), IRF5 (interferon regulatory factor 5), ITGAM (integrin subunit alpha M), LTK (leukocyte tyrosine receptor kinase), NCF2 ( neutrophil cytosolic factor 2), PDCD1 (programmed cell death 1), PTPN22 (protein tyrosine phosphatase, non-receptor type 22), RASGRP1 (RAS guanyl releasing protein 1), RIPK1 (receptor interacting serine / threonine kinase 1), STAT4 (signal transducer and activator of t ranscription 4), TLR5 (Toll like receptor 5), TNFAIP3 (TNF alpha induced protein 3), TNFSF4 (Tumor necrosis factor superfamily member 4) and TREX1 (three prime repair exonuclease 1).
Systemic lupus erythematosus (SLE) and other autoimmune diseases tend to run in families, but the pattern of inheritance is unknown. People can inherit a genetic variation that increases or decreases the risk of SLE but in most cases the condition is not inherited itself. Not all people with SLE have a genetic variation that increases the risk, and not all people with a variation of these genes will develop the disease. In rare cases, the LES may be inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform the detection of mutations associated with systemic lupus erythematosus (SLE), by complete PCR amplification of the exons of BANK1, C4A, C4B, C4B_2, CR2, CRP, CTLA4, Dnase1 genes, DNASE1L3 , FCGR2B, IRF5, ITGAM, LTK, NCF2, PDCD1, PTPN22, RASGRP1, RIPK1, STAT4, TLR5, TNFAIP3, TNFSF4 and TREX1, 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) if postnatal diagnosis. Prenatal diagnosis amniotic liquid.