Anti-topoisomerase antibodies
| Autoantibody | |
|---|---|
| Anti-Topoisomerase | |
| Autoantigen Isoform |
Topoisomerase I (human) |
| Autoantigen gene | TOP1 |
| Affected organ(s) | Dermis |
| Associated Disease(s) |
Scleroderma,
Systemic sclerosis |
| Autoantibody Ig Class |
IgG, IgA |
| DR2 | |
| HLA associations | DR15 |
| DR16 | |
| Other Susceptibility genes |
lymphoid protein tyrosine phos- |
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[1]) is a type of anti-nuclear autoantibody seen mainly in diffuse systemic scleroderma, but is also seen the more limited form of systemic scleroderma called CREST syndrome.[2] However, CREST syndrome is more closely associated with Anti-centromere antibodies.[3] Scl-70 antibodies are associated with more severe scleroderma disease.[4]
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.[5]
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.[6] 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.[7] ATA correlates with rapid progression of disease.[8]
In systemic lupus erythematosus ATA are associated with nephritis.[9]
Increases in ATA+ in scleroderma and SLE are associated with increases in serum CTLA4.[10][11]
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,[12] and in another population study it was found that DR-15 is associated with ATA in systemic sclerosis.[13] 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.[14] The TAP1gene(6p21.3, HLA complex) has also been found in association with ATA+ sclerosis.[15]
References
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- ↑ Table 5-9 in: Lua error in package.lua at line 80: module 'strict' not found. 8th edition.
- ↑ JB Imboden, DB Hellmann, JH Stone. Current Rheumatology Diagnosis & Treatment, Second Edition. McGraw-Hill, 2007.
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