Anti-topoisomerase antibodiesanti-topoisomerase antibodies in blood, anti-topoisomerase antibodies definition
phatase type 22 PTPN22
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
- 1 Epitopes and subtypes
- 2 Pathology
- 3 Genetics
- 4 References
Epitopes and subtypes
Anti Scl-70 antibodies also called anti-topoisomerase I after the type I topoisomerase target 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 However, CREST syndrome is more closely associated with Anti-centromere antibodies 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
Topoisomerase 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 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 ATA are associated with nephritis
Increases in ATA+ in scleroderma and SLE are associated with increases in serum CTLA4
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, 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 1p132 - PTPN22, "CT/TT" genotype showed significant association with anti-topo I The TAP1gene6p213, HLA complex has also been found in association with ATA+ sclerosis
- ^ 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 doi:101007/BF00286991 PMID 2428564
- ^ Table 5-9 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K; Fausto, Nelson 2007 Robbins Basic Pathology Philadelphia: Saunders ISBN 1-4160-2973-7 8th edition
- ^ JB Imboden, DB Hellmann, JH Stone Current Rheumatology Diagnosis & Treatment, Second Edition McGraw-Hill, 2007
- ^ 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 doi:101007/BF02030079 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 doi:101002/art1780330515 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 doi:101016/0014-57938681117-6 PMID 2431927
- ^ Douvas A 1988 "Does Sc1-70 modulate collagen production in systemic sclerosis" Lancet 2 8609: 475–7 doi:101016/S0140-67368890122-5 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:101002/art22747 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:101007/s10067-005-0061-9 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:101093/rheumatology/keh303 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 doi:101002/art1780361013 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:101080/03009740510026751 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:101002/art22196 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:101016/jhumimm200503006 PMID 16112028
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