- Scl-70 antibodies (topoisomerase 1) are a 100-kD nuclear and nucleolar enzyme which are considered to be specific for Scleroderma and are found in nearly 60% of patients having this connective tissue disease. They are more common in patients with interstitial pulmonary fibrosis and extended cutaneous involvement.
- Scl-70 antibodies are a nuclear and nucleolar enzyme that shows nicking‐closing activity on DNA. This nuclear and nucleolar enzyme cuts one strand of a double-stranded DNA at a specific recognition nucleotide sequences that are known as a restriction site. Such enzymes cut only one strand of the DNA duplex and make DNA molecules that are “nicked”, in the place of cleaved.
- Anti–Scl‐70 auto-antibodies are found in approximately 20–35% of patients having systemic sclerosis (SSc), mainly in those with the diffuse form of systemic sclerosis. These antibodies have been usually linked with a poor prognosis that based on medical conditions and also linked to high skin and pulmonary fibrosis.
What Does a Positive SCL 70 Mean?
1. Interpretive Data
Positive Interpretive Data of SCL 70 shows the presence of Scl-70 antibodies in sera which are a considered diagnostic for the presence of scleroderma especially systemic sclerosis (SSc).
Scleroderma is an autoimmune disease or group of autoimmune diseases that may result in skin thickening, scarring of tissue, changes to blood vessels, muscles, and internal organs.
There are two types of scleroderma localized and systemic.
1. Localized Scleroderma
Localized scleroderma is a moderate type of scleroderma. It primarily affects the skin, but it may affect the muscles and bones as well. There are two main types of localized scleroderma: morphea and linear scleroderma.
2. Systemic Scleroderma
Systemic scleroderma shows influences on the whole body, including the blood and internal organs, and especially the esophagus, kidneys, lungs, and heart.
There are two main types of systemic scleroderma: Limited cutaneous systemic sclerosis syndrome (or CREST) and diffuse systemic sclerosis.
- Limited Cutaneous Systemic Sclerosis Syndrome: It is a severe type of systemic scleroderma. It affects the skin on the feet, hands, face, and lower legs and arms. It may create problems within the lungs, blood vessels, and the digestive system.
- Diffuse Systemic Sclerosis: In diffuse systemic sclerosis, the skin becomes thickened and usually affects the area from the hands to above the wrists. It also influences the internal organs.
- Scl-70 antibodies have also been found in many of the patients having systemic lupus erythematosus (SLE). Scl-70 (topo-1) is a DNA binding protein and anti-DNA/DNA complexes in the sera of systemic lupus erythematosus (SLE) patients may connect to topo-I which leads to a false-positive result. The appearance of Scl-70 antibody in sera may also be due to contamination of recombinant Scl-70 antibodies with DNA obtained from cellular material that is used in immunoassays. Strong clinical correlation studies are recommended if both Scl-70 and dsDNA antibodies are detected in sera.
Range Of SCL-70 In Serum
- If the range of SCL-70 is 29 AU/mL or less, the test is negative and consider as a normal range.
- The range between 30-40 AU/mL shows an equivocal result.
- If the range of SCL-70 is 41 AU/mL or greater, the test is positive. This range is considered as an abnormal range and it indicates patient have scleroderma.
Topoisomerase I (SCL 70) Autoantibodies
Autoantibodies against topoisomerase I that are known as anti-Scl 70 antibodies are the typical serologic marker of diffuse systemic sclerosis (dcSSc). In the diffuse systemic sclerosis, skin becomes thickened and usually affects the area from the hands to above the wrists. It also affects the internal organs of the body. The presence of anti-topoisomerase I antibodies is linked with the many severe diseases, particularly with interstitial lung disease.
According to some studies, these antibodies are found in 64% of the patients having diffuse cutaneous SSc (dcSSc) and in 34% of the patient having limited cutaneous systemic sclerosis (lcSSc).
The production of anti-topoisomerase I antibodies seems to be obtained by a self-antigen fragmentation when exposing to the cryptic cellular antigen. But their pathogenic mechanism of action is not clear yet.
Anti-Centromere Antibodies (ACA)
These are autoantibodies which are specific to centromere and kinetochore function. They occur in some autoimmune diseases, generally in limited systemic scleroderma (CREST syndrome), and occasionally in the diffuse type of scleroderma. They are rarely present in other rheumatic conditions and in healthy persons.
Anti-centromere antibodies are found in about 60% of patients having limited systemic scleroderma and in 15% of the patient having the diffuse form of scleroderma. The specificity of this test is greater than 98%. Thus, a positive result of anti-centromere antibodies is strongly indicative of limited systemic scleroderma.
Anti-centromere antibodies primarily present in the course of the disease that notably shows limited cutaneous involvement.
Are Anti-Scl 70 Antibodies and Anti-Centromere Antibodies Mutually Exclusive?
Antibodies that target DNA topoisomerase I (ATA) or centromere proteins (ACA) are associated with clinical studies of patients having systemic sclerosis (SSc).
In clinical studies, both the antibodies were detected by different methods, including enzyme-linked immunosorbent assay, indirect immunofluorescence technique, immunoblot, and immunodiffusion.
Based on clinical studies expression of Anti-Scl 70 antibodies and Anti-centromere antibodies are not totally mutually exclusive, but the coincidence is rare in <1% of patients with systemic scleroderma.