Anti-topoisomerase antibodies

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Autoantibody
Anti-Topoisomerase
Autoantigen
Isoform
Topoisomerase I (human)
Autoantigen gene TOP1
Affected organ(s) Dermis
Associated
Disease(s)
Scleroderma,

Systemic sclerosis

Autoantibody
Ig Class
IgA
DR2
HLA associations DR15
DR16
Other
Susceptibility
genes
lymphoid protein

tyrosine phos-
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).

Epitopes and subtypes

anti-topoisomerase I after the type I topoisomerase target[1]) is a type of antinuclear 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 antinuclear 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 TAP1 gene (6p21.3, HLA complex) has also been found in association with ATA+ sclerosis.[15]

References