Anti-topoisomerase antibodies
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| Autoantibody(s) | |
|---|---|
| Anti-Topoisomerase | |
| Autoantigen Isoform | Topoisomerase I (human) |
| Autoantigen gene | TOP1 |
| Affected organ(s) | Dermis |
| AssociatedDisease(s) | Scleroderma,
Systemic sclerosis |
| AutoantibodyIg Class | IgG, IgA |
| DR2 | |
| HLA associations | DR15 |
| DR16 | |
| OtherSusceptibilitygenes | lymphoid protein
tyrosine phos- phatase type 22 PTPN22 |
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Anti-topoisomerase antibodies (ATA) are 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 is recognized as one of two major classes of autoantibodies in sclerosis[1] (systemic or scleroderma). The antigen of Anti Scl-70 was recognized as topoisomerase I in 1986[1] with anti-centromere antibodies constituting the other class. ATA is associated with more severe disease.[1]
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.[1]
Pathology
Topoisomerase I is an enzyme that relaxes the strain on DNA by nicking and ligating the DNA. ATA inhibits the activity of this enzyme.[1] Since this activity occurs in the nucleus of the cell ATA is a form of anti-nuclear antibody. 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.[1] ATA correlates with rapid progression of disease.[1]
In systemic lupus erythematosus ATA are associated with nephritis.[1]
Increases in ATA+ in scleroderma and SLE are associated with increases in serum CTLA4.[1][1]
Genetics
HLA-DR2 (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 HLA-DR2,[1], and in another population study it was found that DR-15 is associated with ATA in systemic sclerosis.[1] In addition to HLA-DR, the protein tyrosine phosphatase, non-receptor type 22 (lymphoid) (1p13.2 - PTPN22), "CT/TT" genotype showed significant association with anti-topo I.[1] The TAP1gene(6p21.3, HLA complex) has also been found in association with ATA+ sclerosis.[1]
References
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
