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Anti-topoisomerase Antibodies
Anti-topoisomerase antibodies (ATA) are autoantibodies directed against topoisomerase and found in several diseases, most importantly scleroderma. Diseases with ATA are autoimmune disease because they react with self-proteins. They are also referred to as anti-DNA topoisomerase I antibody (anti-topo I). Epitopes and subtypes Anti Scl-70 antibodies (also called '' anti-topoisomerase I'' after the type I topoisomerase target) is a type of antinuclear autoantibody seen mainly in diffuse systemic scleroderma, but is also seen the more limited form of systemic scleroderma called CREST syndrome.Table 5-9 in: 8th edition. However, CREST syndrome is more closely associated with anti-centromere antibodies.JB Imboden, DB Hellmann, JH Stone. Current Rheumatology Diagnosis & Treatment, Second Edition. McGraw-Hill, 2007. Scl-70 antibodies are associated with more severe scleroderma disease. Anti-topoisomerase antibodies can be classified according to their immunoglobulin class (IgM, IgG or ...
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Scleroderma
Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure. One form of the condition, known as CREST syndrome, classically results in calcium deposits, Raynaud's syndrome, esophageal problems, thickening of the skin of the fingers and toes, and areas of small, dilated blood vessels. The cause is unknown, but it may be due to an abnormal immune response. Risk factors include family history, certain genetic factors, and exposure to silica. The underlying mechanism involves the abnormal growth of connective tissue, which is believed to be the result of the immune system attacking healthy tissues. Diagnosis is based on symptoms, supported by a skin biopsy or blood tests. While no cure ...
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Type I Topoisomerase
In molecular biology Type I topoisomerases are enzymes that cut one of the two strands of double-stranded DNA, relax the strand, and reanneal the strand. They are further subdivided into two structurally and mechanistically distinct topoisomerases: type IA and type IB. * Type IA topoisomerases change the linking number of a circular DNA strand by units of strictly 1. * Type IB topoisomerases change the linking number by multiples of 1 (n). Historically, type IA topoisomerases are referred to as prokaryotic topo I, while type IB topoisomerases are referred to as eukaryotic topoisomerase. This distinction, however, no longer applies as type IA and type IB topoisomerases exist in all domains of life. Functionally, these subclasses perform very specialized functions. Prokaryotic topoisomerase I (topo IA) can only relax negative supercoiled DNA, whereas eukaryotic topoisomerase I (topo IB) can introduce positive supercoils, separating the DNA of daughter chromosomes after DNA r ...
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Chromosome 6
Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans nearly 171 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total DNA in cells. It contains the major histocompatibility complex, which contains over 100 genes related to the immune response, and plays a vital role in organ transplantation. The evolution of human centromere 6 The centromere of chromosome 6 illustrates an interesting example of centromere evolution. It was known that in a Catarrhini ancestor the chromosome 6 centromere was situated near position 26 Mb of the modern human chromosome. In ''Macaca mulatta'', this old centromere went defunct and repositioned to a different chromosomal location. In the case of humans, the old centromere went defunct and a more recent form emerged near the modern position of human cen6 (size of 60 Mb). Such cases are known as Evolutionary New Centromeres (ENC). ...
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Chromosome 1
Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which are the basic units of information for DNA.http://vega.sanger.ac.uk/Homo_sapiens/mapview?chr=1 Chromosome size and number of genes derived from this database, retrieved 2012-03-11. It represents about 8% of the total DNA in human cells. It was the last completed chromosome, sequenced two decades after the beginning of the Human Genome Project. Genes Number of genes The following are some of the gene count estimates of human chromosome 1. Because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies (for technical details, see gene prediction). Among various projects, the collaborative consensus coding sequence project ( CCDS) takes an extremely conservative strategy. S ...
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Systemic Lupus Erythematosus
Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms. Children up to 18 years old develop a more severe form of SLE termed childhood-onset systemic lupus erythematosus. The cause of SLE is not clear. It is thought to involve a combination of genetics and environmental factors. Among identical twins, if one is affected there is a 24% chance the other one will also develop the disease. Female sex hormones, sunlight, smoking, vitamin D deficiency, and certain infections are also believed to increa ...
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Antinuclear Antibody
Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some cases, antibodies to human antigens are produced; these are known as autoantibodies. There are many subtypes of ANAs such as anti-Ro antibodies, anti-La antibodies, anti-Sm antibodies, anti-nRNP antibodies, anti-Scl-70 antibodies, anti-dsDNA antibodies, anti-histone antibodies, antibodies to nuclear pore complexes, anti-centromere antibodies and anti-sp100 antibodies. Each of these antibody subtypes binds to different proteins or protein complexes within the nucleus. They are found in many disorders including autoimmunity, cancer and infection, with different prevalences of antibodies depending on the condition. This allows the use of ANAs in the diagnosis of some autoimmune disorders, including system ...
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Topoisomerase I
DNA topoisomerase 1 is an enzyme that in humans is encoded by the ''TOP1'' gene. It is a DNA topoisomerase, an enzyme that catalyzes the transient breaking and rejoining of a single strand of DNA. Function This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which lets the broken strand rotate around the intact strand, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. Mechanism As reviewed by Champoux, the type IB topoisomerases, including TOP1, form a covalent intermediate in which the active site tyrosine becomes attached to the 3' phosphate end of the cleaved strand rather than the 5' phosphate end. The eukaryotic topoisomerases I were found to nick the DNA with a preference for a sequence of nucleotides that extends from positions -4 t ...
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Anti-centromere Antibodies
Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some cases, antibodies to human antigens are produced; these are known as autoantibodies. There are many subtypes of ANAs such as anti-Ro antibodies, anti-La antibodies, anti-Sm, anti-Sm antibodies, anti-nRNP, anti-nRNP antibodies, anti-Scl-70 antibodies, anti-dsDNA antibodies, anti-histone antibodies, antibodies to nuclear pore complexes, anti-centromere antibodies and sp100 nuclear antigen, anti-sp100 antibodies. Each of these antibody subtypes binds to different proteins or protein complexes within the nucleus. They are found in many disorders including autoimmunity, cancer and infection, with different prevalences of antibodies depending on the condition. This allows the use of ANAs in the diagnosis of some au ...
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CREST Syndrome
CREST syndrome, also known as the limited cutaneous form of systemic sclerosis (lcSSc), is a multisystem connective tissue disease, connective tissue disorder. The acronym "CREST" refers to the five main features: calcinosis, Raynaud's phenomenon, Esophageal motility disorder, esophageal dysmotility, sclerodactyly, and telangiectasia. CREST syndrome is associated with detectable antibodies against centromeres (a component of the cell nucleus), and usually spares the kidneys (a feature more common in the related condition systemic scleroderma). If the lungs are involved, it is usually in the form of pulmonary arterial hypertension. Signs and symptoms Calcinosis CREST causes thickening and tightening of the skin with deposition of calcific nodules ("calcinosis"). Raynaud's phenomenon Raynaud's phenomenon is frequently the first manifestation of CREST/lcSSc, preceding other symptoms by years. Stress and cold temperature induce an exaggerated vasoconstriction of the small arter ...
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Systemic Scleroderma
Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two major subgroups of systemic sclerosis based on the extent of skin involvement: limited and diffuse. The limited form affects areas below, but not above, the elbows and knees with or without involvement of the face. The diffuse form also affects the skin above the elbows and knees and can also spread to the torso. Visceral organs, including the kidneys, heart, lungs, and gastrointestinal tract can also be affected by the fibrotic process. Prognosis is determined by the form of the disease and the extent of visceral involvement. Patients with limited systemic sclerosis have a better prognosis than those with the diffuse form. Death is most often caused by lung, heart, and kidney involvement. The risk of cancer is increased slightly. S ...
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Antinuclear Antibody
Antinuclear antibodies (ANAs, also known as antinuclear factor or ANF) are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some cases, antibodies to human antigens are produced; these are known as autoantibodies. There are many subtypes of ANAs such as anti-Ro antibodies, anti-La antibodies, anti-Sm antibodies, anti-nRNP antibodies, anti-Scl-70 antibodies, anti-dsDNA antibodies, anti-histone antibodies, antibodies to nuclear pore complexes, anti-centromere antibodies and anti-sp100 antibodies. Each of these antibody subtypes binds to different proteins or protein complexes within the nucleus. They are found in many disorders including autoimmunity, cancer and infection, with different prevalences of antibodies depending on the condition. This allows the use of ANAs in the diagnosis of some autoimmune disorders, including system ...
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Anti-topoisomerase I
Anti-Scl-70 (also called anti-topoisomerase I after the type I topoisomerase target) is an anti-topoisomerase antibody-type of anti-nuclear autoantibodies, seen mainly in diffuse systemic scleroderma (with a sensitivity of 28–70%), but is also seen in 10–18% of cases of the more limited form of systemic scleroderma called CREST syndrome.Table 5-9 in: 8th edition. Anti Scl-70 antibodies are associated with more severe scleroderma disease. The etymology of scl-70 consists of an abbreviation of scleroderma and a 70 kD extractable immunoreactive fragment that can be obtained from the otherwise larger (100–105 kD) target topoisomerase antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ... (called the SCL-70 Antigen) of the antibodies.
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