Anti-topoisomerase antibodies
From Wikipedia, the free encyclopedia
| Autoantibody(s) | |
|---|---|
| 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).
Contents |
[edit] 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[2] with anti-centromere antibodies constituting the other class. ATA is associated with more severe disease.[3]
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.[4]
[edit] 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.[5] 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.[6] ATA correlates with rapid progression of disease.[7]
In systemic lupus erythematosus ATA are associated with nephritis.[8]
Increases in ATA+ in scleroderma and SLE are associated with increases in serum CTLA4.[9][10]
[edit] 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,[11], and in another population study it was found that DR-15 is associated with ATA in systemic sclerosis.[12] 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.[13] The TAP1gene(6p21.3, HLA complex) has also been found in association with ATA+ sclerosis.[14]
[edit] References
- ^ Catoggio LJ, Skinner RP, Maddison PJ (1983). "Frequency and clinical significance of anticentromere and anti Scl-70 antibodies in an English connective tissue disease population". Rheumatol. Int. 3 (1): 19-21. PMID 6412349.
- ^ Guldner HH, Szostecki C, Vosberg HP, Lakomek HJ, Penner E, Bautz FA (1986). "Scl 70 autoantibodies from scleroderma patients recognize a 95 kDa protein identified as DNA topoisomerase I". Chromosoma 94 (2): 132-8. PMID 2428564.
- ^ de Rooij DJ, Van de Putte LB, Habets WJ, Van Venrooij WJ (1989). "Marker antibodies in scleroderma and polymyositis: clinical associations". Clin. Rheumatol. 8 (2): 231-7. PMID 2547546.
- ^ Hildebrandt S, Weiner E, Senécal JL, et al (1990). "The IgG, IgM, and IgA isotypes of anti-topoisomerase I and anticentromere autoantibodies". Arthritis Rheum. 33 (5): 724-7. PMID 2161233.
- ^ Samuels DS, Tojo T, Homma M, Shimizu N (1986). "Inhibition of topoisomerase I by antibodies in sera from scleroderma patients". FEBS Lett. 209 (2): 231-4. PMID 2431927.
- ^ Douvas A (1988). "Does Sc1-70 modulate collagen production in systemic sclerosis?". Lancet 2 (8609): 475-7. PMID 2900403.
- ^ Perera A, Fertig N, Lucas M, et al (2007). "Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody". Arthritis Rheum. 56 (8): 2740-6. doi:. PMID 17665460.
- ^ Hamidou MA, Audrain MA, Masseau A, Agard C, Moreau A (2006). "Anti-topoisomerase I antibodies in systemic lupus erythematosus as a marker of severe nephritis". Clin. Rheumatol. 25 (4): 542-3. doi:. PMID 16525896.
- ^ Sato S, Fujimoto M, Hasegawa M, et al (2004). "Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis". Rheumatology (Oxford, England) 43 (10): 1261-6. doi:. PMID 15266059.
- ^ Takeuchi F, Kawasugi K, Nabeta H, Mori M, Tanimoto K (2002). "Association of CTLA-4 with systemic sclerosis in Japanese patients". Clin. Exp. Rheumatol. 20 (6): 823-8. PMID 12508774.
- ^ Kuwana M, Kaburaki J, Mimori T, Tojo T, Homma M (1993). "Autoantigenic epitopes on DNA topoisomerase I. Clinical and immunogenetic associations in systemic sclerosis". Arthritis Rheum. 36 (10): 1406-13. PMID 7692859.
- ^ Joung CI, Jun JB, Chung WT, et al (2006). "Association between the HLA-DRB1 gene and clinical features of systemic sclerosis in Korea". Scand. J. Rheumatol. 35 (1): 39-43. doi:. PMID 16467040.
- ^ Gourh P, Tan FK, Assassi S, et al (2006). "Association of the protein tyrosine phosphatase, non-receptor type 8 R620W polymorphism with anti-topoisomerase I- and anticentromere antibody-positive systemic sclerosis". Arthritis Rheum. 54 (12): 3945-53. doi:. PMID 17133608.
- ^ Song YW, Lee EB, Whang DH, Kang SJ, Takeuchi F, Park MH (2005). "Association of TAP1 and TAP2 gene polymorphisms with systemic sclerosis in Korean patients". Hum. Immunol. 66 (7): 810-7. doi:. PMID 16112028.
