Anti-topoisomerase antibodies
Encyclopedia
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).
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
. Anti 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.
. 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.
(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) (1p13.2 - ), "CT/TT" genotype showed significant association with anti-topo I. The gene(6p21.3, HLA
complex) has also been found in association with ATA+ sclerosis.
Topoisomerase
Topoisomerases are enzymes that regulate the overwinding or underwinding of DNA. The winding problem of DNA arises due to the intertwined nature of its double helical structure. For example, during DNA replication, DNA becomes overwound ahead of a replication fork...
and found in several diseases, most importantly scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
. Diseases with ATA are autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
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 topoisomeraseType I topoisomerase
Type I topoisomerases cut one strand of double-stranded DNA, relax the strand, and reanneal the strands. They are further subdivided into two structurally and mechanistically distinct topoisomerases: type IA and type IB....
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
CREST syndrome
The limited cutaneous form of systemic scleroderma is often referred to as CREST syndrome. "CREST" is an acronym for the five main features:* Calcinosis* Raynaud's syndrome* Esophageal dysmotility* Sclerodactyly* Telangiectasia...
. Anti 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.
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. Since this activity occurs in the nucleus of the cell ATA is a form of anti-nuclear antibodyAnti-nuclear antibody
Anti-nuclear antibodies are autoantibodies directed against contents of the cell nucleus....
. 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
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
ATA are associated with nephritis.
Increases in ATA+ in scleroderma and SLE are associated with increases in serum CTLA4.
Genetics
HLA-DR2HLA-DR2
HLA-DR2 of the HLA-DR serotype system, is a broad antigen serotype that is now preferentially covered by HLA-DR15 and HLA-DR16 serotype group...
(DR15
HLA-DR15
HLA-DR15 is a HLA-DR serotype that recognizes the DRB1*1501 to *1505 and *1507 gene products. DR15 is found at high levels from Ireland to Central Asia. frequencies...
and DR16
HLA-DR16
HLA-DR16 is a HLA-DR serotype that recognizes the DRB1*1601, *1602 and *1604 gene products. DR16 is found in the Mediterranean at modest frequencies...
) 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
HLA-DR2
HLA-DR2 of the HLA-DR serotype system, is a broad antigen serotype that is now preferentially covered by HLA-DR15 and HLA-DR16 serotype group...
,, 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) (1p13.2 - ), "CT/TT" genotype showed significant association with anti-topo I. The gene(6p21.3, HLA
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
complex) has also been found in association with ATA+ sclerosis.