Single Analytes 2
Autoantibodies against
ssDNA NEW! | Histones (IgG/IgM) | Scl-70 | CENP | PM-Scl | Jo-1
ssDNA
Product
|
Article No.
|
No. of tests
|
EliA ssDNA NEW! |
14562901 |
2 x 12 tests |
Varelisa ssDNA Antibodies |
148 96 |
96 tests |
Promotion Material
Performance Folder
EliA ssDNA (pdf)
Antigen
In 1971 Cohen et al. proposed three categories of antibodies directed against the DNAmolecule:
- The first category is directed against conformational epitopes associated with the native doublehelical structure. By definition these DNA antibodies are the only true dsDNA antibodies. However, they seem to be rare.
- The second group targets the polymers of purine and pyrimidine bases, which as antigens are accessible to the immunocompetent cells only in the singlestranded DNA, i.e. in the denatured state. These antibodies are considered the only true ssDNA antibodies.
- The third group targets the desoxyribose-phosphate backbone, which is equally present in ssDNA and dsDNA molecules. Accordingly they are neither true dsDNA nor ssDNA antibodies. The majority (85 to 95%) of DNA antibodies in patient samples belongs to this category.
From a technical point of view it is impossible to measure in a single test true ssDNA antibodies (with purine and pyrimidine bases being the sole antigen). All ssDNA antibodies tests measure DNA antibodies belonging to category 2 and 3.
In both assays, the EliA ssDNA and the Varelisa assay, the plate is coated with synthetic single stranded DNA.
Disease association, antibody prevalence and specificity
- ssDNA antibodies are commonly found in SLE and drug-induced lupus (DIL).
- Antibodies against ssDNA occur in 50-70 % of SLE.
- Together with histone antibodies and in the absence of dsDNA antibodies they aid in the diagnosis of DIL.
- They occur in approx. 25% of discoid lupus and are often linked to the photosensitive cutaneous SLE subtype.
- They may serve as a risk indicator for developing systemic features.
- However, they are not specific as they occur in systemic and localized scleroderma, liver disorders, a number of connective tissue diseases and some healthy individuals, too.
- The antibodies correlate with disease activity and with the response to drug therapy in SLE (43% in inactive SLE, up to 87% in active SLE).
When is the measurement recommended?
Suspicion of SLE or drug-induced lupus.
Antibody isotypes
IgG
References
Takehara K et al.
| Kofler D et al. (1973)
| Ruffati A et al. (1991)
| Lange A.
| Chang C et al (2011)
| Provost TT et al. (1985)
| Maddison PJ et al. (1981)
| Okamura M et al. (1993)
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Histones
Product
|
Article No.
|
No. of tests
|
Varelisa Histone (IgG/IgM) Antibodies |
164 96 |
96 tests |
Antigen
As an autoimmune disease SLE is characterized by a complex clinical picture and by a great diversity of autoantibodies. Antibodies against dsDNA and RNP-Sm are the most prominent ones in the diagnosis of SLE since they demonstrate high specificity for the disease. Of comparable prevalence are antibodies against DNA binding histone proteins (H1, H2A/H2B, H3 and H4). They can be found in up to 50 % of all SLE patient sera. Their frequency increases to 80 % in patients with the acute disease. Anti Histone Antibodies (AHA) are of clinical importance for the diagnosis of drug-induced lupus erythematosus. Drugs such as hydralazine, procainamide and isoniazide are known for their LE inducing effect. In addition to antibodies against single histones, antibodies against histone complexes such as H2A-H2B and H3-H4 are frequently found in DIL. Dependent on the inducing drug, up to 90-95 % of DIL patients are positive for histone autoantibodies. However, the test is of limited value as these antibodies are found in other diseases such as infections. AHA have also been found in patients with rheumatoid arthritis, mixed connective tissue disease and progressive scleroderma. The incidence of AHA in these patients however is low ranging from 10 to 15 percent.
In the Varelisa assay the plate is coated with purified human histone proteins H1, H2A, H2B, H3 and H4.
When is the measurement recommended?
Suspicion of drug-induced lupus.
Antibody isotypes
IgG and IgM (measured with mixed conjugate)
Detection methods
Enzyme-linked immunosorbent assays (ELISA).
References
Rubin R.
| Harmon CE, Portanova JP
| Shoenfeld Y, Segol O.
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Scl-70 / DNA topoisomerase I
Products
|
Article No.
|
No. of tests
|
Varelisa Scl-70 Antibodies |
169 96 |
96 tests |
EliA Scl-70 |
14-5506-01 |
2x12 tests |
Promotion Material
Antigens
In 1979 antibodies of scleroderma patients where described, which react with a 70 kDa protein. Thus, the antigen was named Scl-70. In 1986, Scl-70 was identified as topoisomerase I (topo-I). Topoisomerase I catalyzes the breaking/rejoining of single-stranded DNA and relaxes supercoiled DNA in vitro. The native enzyme is larger than 70 kDa (100 kDa) but often only its smaller proteolytic fragment is found.
The Varelisa Scl-70 Antibodies assay and the EliA Scl-70 Wells are coated with a human, recombinant Topoisomerase I antigen.
Disease association, antibody prevalence and specificity
- Scleroderma (30-60 %), highly specific
- Anti-Scl-70 do not exclude additional AI disorders like SLE, Sjögren's syndrome etc.
- Not present in relatives of scleroderma patients or other healthy individuals
- Rarely found in Raynaud's syndrome, but than often as predictor of scleroderma
Information about Scleroderma
Anti-Scl-70 are rarely found in the same patients as anti-centromere antibodies.
Disease activity
Most studies found, that titer does not correlate with disease activity or duration. However, there is evidence, that anti-Scl-70 levels correlate with disease severity and activitiy in systemic sclerosis (see reference Hu et al., 2003).
When is the measurement recommended?
Suspicion of scleroderma.
Antibody isotypes
IgG
References
Vazquez-Abad D, Rothfield NF (1996)
| Verheijen R (1996)
| Spencer-Green G, Alter D, Welch HG (1997)
| Hu PQ, Fertig N, Medsger TA, Wright TM (2003)
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Centromere Protein (CENP)
Products
|
Article No.
|
No. of tests
|
Varelisa CENP Antibodies |
168 96 |
96 tests |
EliA CENP |
14-5505-01 |
2x12 tests |
Promotion Material
Antigens
The centromere is the primary constriction site of eukaryotic chromosomes where sister chromatids appear most tightly paired. The three main centromere antigens are CENP-A (19 kDa), CENP-B (80 kDa) and CENP-C (140 kDa) but the most important centromere antigen is the CENP-B. Antibodies to CENP-A and -C are usually cross-reacting and are found almost always in combination with anti-CENP-B antibodies. CENP-B is recognized by virtually all sera with anti-centromere antibodies (ACA).
CENP-B is located within the heterochromatin underneath the kinetochore and probably forms a dimer that binds DNA and has an important role in regulating higher order chromatin structure within the centromere.
The Varelisa CENP Antibodies assay and the EliA CENP Well are coated with human recombinant CENP-B.
Disease association, antibody prevalence and specificity
- CREST (about 55 %)
- Raynaud's disease (10-15 %)
- Diffuse systemic scleroderma (very rarely - ACA in SSc indicate a significantly better prognosis)
- Other rheumatic conditions with Raynaud's phenomenon, e.g. rheumatoid arthritis, Sjögren's syndrome etc. (33 %)
- Primary biliary cirrhosis (PBC) (10-20 %)
- Not found in healthy individuals, even in low titers (or extremely rare)
ACA are rarely found in the same patients as anti-Scl-70
Disease activity
The titer does not correlate with disease activity or duration.
When is the measurement recommended?
Raynaud's syndrome, suspicion or diagnosis of scleroderma, primary biliary cirrhosis.
Antibody isotype
IgG
References
McHugh NJ (1996)
| Rothfield NF (1996)
| Spencer-Green G, Alter D, Welch HG (1997)
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PM-Scl NEW!
Product
|
Article No.
|
No. of tests
|
Elia PM-Scl |
14-5602-01 |
2x12 tests |
Promotion Material
EliA PM-Scl (pdf)
Antigens
EliA PM-Scl is coated with human recombinant PM-Scl antigen.
Disease association, antibody prevalence and specificity
- 24 % of patients with PM/SSc overlap syndrome
- 8 % of patients with polymyositis
- 3 % of patients with scleroderma
Prevalence in controls (specificity)
Most papers state a very high specificity, however, also frequent co-occurrence in DNA-positive SLE patients is described.
Indications of a positive PM-Scl result
App. 70% of PM-Scl-positive patients have PM/SSc overlap, app. 20% have idiopathic myositis and app. 10% have scleroderma.
Disease activity
The antibody usually remains detectable throughout the course of disease, and indefinitely thereafter despite control of disease activity. Occasionally, the antibody becomes undetectable. The clinical utility of anti-PM-Scl antibody fluctuation requires further investigation.
When is the measurement recommended?
- Suspicion of polymyositis/scleroderma (PM/SSc) overlap syndrome
- Suspicion of systemic sclerosis
- Suspicion of childhood scleromyositis
- Diagnosis / differential diagnosis of myositis of unclear origin
Antibody isotype
IgG
References
Conrad K et al (2002)
| Walker JG, Fritzler MJ (2007)
| Mahler M et al (2009)
| Jaskowski TD et al (2011)
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Jo-1 / Histidyl-tRNA-Synthetase
Products
|
Article No.
|
No. of tests
|
Varelisa Jo-1 Antibodies |
167 96 |
96 tests |
Elia Jo-1 |
14-5507-01 |
2x12 tests |
Promotion Material
Performance Folder
EliA ANA Differentiation (pdf)
Sm, U1RNP, RNP70, RO, La, Scl-70, CENP, Jo-1
Antigens
Jo-1 is synonymous with histidyl tRNA synthetase. This cytoplasmic enzyme catalyzes the esterification of histidine to its cognate tRNA. Binding of anti-Jo-1 antibodies is localized to the cytoplasm of the various cell types examined. Histidyl tRNA synthetase is persent as a homodimer within the cell; identical subunits of approximately 50 kDa are each bound to tRNA. Anti-Jo-1 sera only recognize histidyl-tRNA synthetases and no other aminoacyl-tRNA synthetases. They only react with histidyl-tRNA syntheases from higher eukaryotes. The greatest affinity is present with the human protein.
The Varelisa Jo-1 Antibodies assay and the EliA Jo-1 Well are coated with human recombinant Jo-1.
Disease association, antibody prevalence and specificity
Disease activity
The antibody usually remains detectable throughout the course of disease, and indefinitely thereafter despite control of disease activity. Occasionally, the antibody becomes undetectable, and in those cases it was assocaited with remission of disease. The clinical utility of anti-Jo-1 antibody fluctuation requires further investigation.
Although it would be extremely unusual for anti-Jo-1 antibodies to develop in a patient who was previously negative for the antibody, repeat testing of such a patient might be considered in order to confirm the accuracy of the previous result in a suggestive clinical situation, such as myositis with interstitial lung disease. In a patient found to be positive, besides confirmatory testing if question exist, repeat testing might be considered as treatment is being discontinued, since the risk of reexacerbation is high if the antibody persists.
When is the measurement recommended?
Suspicion of any kind of myositis.
Antibody isotype
IgG
References
Maddison PJ (1996)
| Targoff IN, Plotz PH (1996)
| Delarue M (1995)
| Targoff IN (1992)
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