Single Analytes 2
Autoantibodies against
ssDNA | Histones (IgG/IgM) | Scl-70 | CENP | PM-Scl | Jo-1
ssDNA
Product
|
Article No.
|
No. of tests
|
Varelisa ssDNA Antibodies |
148 96 |
96 tests |
Antigen
In 1971, Cohen et al. proposed three categories of antibodies directed against the DNA molecule:
- The first is directed against conformational epitopes associated with the native double-helical structure. By definition, these DNA antibodies are the only true dsDNA antibodies. However, they seem to be rare.
- The second targets the polymers of purine and pyrimidine bases, which as antigens are accessible to the immunocompetent cells only in single-stranded DNA, i.e. in the denatured state. These antibodies are considered the only true ssDNA antibodies.
- The third targets the desoxyribose-phosphate backbone, which is equally present in ssDNA and dsDNA molecules. Accordingly, they are neither true dsDNA nor true ssDNA antibodies. The majority (85-95%) of DNA antibodies in patient samples belong to this category.
From a technical point of view, it is impossible to measure true ssDNA antibodies (with purine and pyrimidine bases being the sole antigens) in a single test. All ssDNA antibody tests measure DNA antibodies belonging to categories 2 and 3. ssDNA antibodies are commonly found in SLE and drug-induced lupus (DIL). Together with histone antibodies, and in the absence of dsDNA antibodies, they may be an aid in the diagnosis of DIL. They are not specific, however, but also occur in systemic and localized scleroderma, liver disorders, a number of connective tissue diseases and some normal individuals.
In the Varelisa assay, the plate is coated with synthetic single-stranded DNA.
When is the measurement recommended?
Suspicion of SLE or drug-induced lupus.
Antibody isotypes
IgG
Detection methods
Enzyme-linked immunosorbent assays (ELISA).
References
Takehara K et al.
| Ruffati A et al.
| Lange A.
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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 in the diagnosis of SLE because 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. Depending on the inducing drug, up to 90-95% of DIL patients are positive for histone autoantibodies. However, the test is of limited value because 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. However, the incidence of AHA in these patients is low, ranging from 10-15%.
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 were described that react with a 70 kDa protein. The antigen was therefore named Scl-70. In 1986, Scl-70 was identified as topoisomerase I (topo-I). Topoisomerase I catalyses 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 such as SLE, Sjögren's syndrome, etc.
- Not present in relatives of scleroderma patients or other healthy individuals
- Rarely found in Raynaud's syndrome, but then often as a predictor of scleroderma
Information about scleroderma
Anti-Scl-70 are rarely found with anti-centromere antibodies in the same patient.
Disease activity
Most studies found that titre does not correlate with disease activity or duration. However, there is evidence that anti-Scl-70 levels correlate with disease severity and activity 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), the most important being CENP-B. Antibodies to CENP-A and -C are usually cross-reacting and are almost always found 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 titres (or extremely rare)
ACA are rarely found with anti-Scl-70 in the same patient
Disease activity
The titre does not correlate with the 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, frequent co-occurrence in DNA-positive SLE patients is also described.
Indications of a positive PM-Scl result
Approx. 70% of PM-Scl-positive patients have PM/SSc overlap, approx. 20% have idiopathic myositis and approx. 10% have scleroderma.
Disease activity
The antibody usually remains detectable throughout the course of the 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 catalyses 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 present 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 synthetases from higher eukaryotes. The greatest affinity is 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, in which cases it is associated 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 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, in addition to confirmatory testing if there is any doubt, repeat testing might be considered when treatment is discontinued, because 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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