Anti-topoisomerase antibodies (ATA) are

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...

directed against

topoisomerase DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues i ...

and found in several diseases, most importantly

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 ...

. Diseases with ATA are

autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

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 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 s ...

'' after the

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 topoisomerase ...

target) is a type of

anti-nuclear autoantibody 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 prote ...

seen mainly in diffuse

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 m ...

, but is also seen the more limited form of systemic scleroderma called

CREST syndrome CREST syndrome, also known as the limited cutaneous form of systemic sclerosis (lcSSc), is a multisystem connective tissue disorder. The acronym "CREST" refers to the five main features: calcinosis, Raynaud's phenomenon, esophageal dysmotility, s ...

.Table 5-9 in: 8th edition. However, CREST syndrome is more closely associated with

anti-centromere antibodies Anti-centromere antibodies (ACAs; often styled solid, anticentromere) are autoantibodies specific to centromere and kinetochore function. They occur in some autoimmune diseases, frequently in limited systemic scleroderma (formerly called CREST s ...

.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 IgA). IgG-ATA is found most frequently in scleroderma, with IgA being quite common but IgM very infrequent.

Pathology

Topoisomerase I DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues i ...

is an enzyme that relaxes the strain on DNA by nicking and ligating the DNA. ATA inhibits the activity of this enzyme. Since this activity occurs in the nucleus of the cell ATA is a form of

anti-nuclear 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 pro ...

. Scleroderma results from the overproduction of collagen in affected tissues, one study claims that there is an increased density of Topoisomerase I sites in the collagen genes, and that the antibodies may be altering transcription at these loci. ATA correlates with rapid progression of disease. In

systemic lupus erythematosus Lupus, technically known as 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. Comm ...

ATA are associated with nephritis. Increases in ATA+ in scleroderma and SLE are associated with increases in serum CTLA4.

Genetics

HLA-DR2 HLA-DR2 (DR2) of the HLA- DR serotype system, is a broad antigen serotype that is now preferentially covered by HLA-DR15 and HLA-DR16 serotype group. This serotype primarily recognizes gene products of the HLA-DRB1*15 and HLA-DRB1*16 allele gro ...

( DR15 and DR16) are associated with Scleroderma and systemic sclerosis. It has been found that patients with ATA that recognize the ET4 domain of topoisomerase were frequently

, and in another population study it was found that DR-15 is associated with ATA in systemic sclerosis. In addition to HLA-DR, the ''protein tyrosine phosphatase, non-receptor type 22 (lymphoid)'' ( 1p13.2 - ), "CT/TT" genotype showed significant association with anti-topo I. The gene ( 6p21.3, HLA complex) has also been found in association with ATA+ sclerosis.

References

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