Evaluating patients suspected of having systemic sclerosis as part of systemic sclerosis criteria antibody tests.
Providing diagnostic and prognostic information in patients with systemic sclerosis.
A positive result indicates detectable anti-RNA polymerase III above assay cutoff and does not unequivocally establish a diagnosis of systemic sclerosis.
Enzyme immunoassay to detect anti-RNA polymerase III antibody uses an immunodominant epitope as antigen. Negative result does not also rule out the presence of antibodies targeting other epitopes in the RNA polymerase I/III antigens.
The level of RNA polymerase III autoantibodies does not indicate the severity of disease in patients with systemic sclerosis (SSc). However, patients with high positive anti-RNA polymerase III antibody titers are more likely to have SSc compared to those with low antibodies.
Anti-RNA polymerase III antibodies may occur prior to clinical onset of SSc.
The presence of immune complexes or other immunoglobulin aggregates in the patient specimen may cause an increased level of nonspecific binding and produce false-positive results with this assay.
Systemic sclerosis (SSc) is a multisystem autoimmune connective tissue disease characterized by vascular dysfunction, fibrotic changes in the skin and internal organs as well as an autoimmune response manifested by production of diverse antibodies. While the clinical manifestations and severity of SSc are highly variable, two main subsets are widely recognized. These include the limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) subtypes of which the diffuse form has the worse prognosis and survival rates. Immunologically, SSc is characterized by the presence of several disease-specific and mutually exclusive autoantibodies considered helpful in the diagnosis, stratification, and prognosis of disease. Of the described autoantibodies, the 2013 American College of Rheumatology/European League against Rheumatism classification criteria for SSc recommends testing for centromere, topoisomerase I (topo I or Scl 70), and RNA polymerase III autoantibodies. Antibodies to Scl 70 and RNA polymerase III are generally associated with dcSSc while those to centromere typically correlate with the lcSSc form of disease.
The human nuclei consist of three RNA polymerases, RNA polymerase I, II and III. Of these, antibodies targeting RNA polymerases I and III are always present together and are most common in patients with SSc. The RPC155 immunodominant epitope has been identified in autoantibodies associated with anti-RNA polymerase I/III in patients with SSc and is widely used in solid-phase immunoassays for the detection and quantification of anti-RNA polymerase III antibodies in clinical laboratories.
The prevalence of anti-RNA polymerase III antibodies in patients with SSc is variable with a pooled prevalence of 11% and ranges from 0 to 41% in different studies. This variability may be due to environmental and genetic factors as well as lack of harmonization of immunoassays for the detection of antibodies. Positivity for anti-RNA polymerase III antibody is generally mutually exclusive of other SSc-specific antibodies such as centromere and Scl 70. In addition, SSc patients who test positive for anti-RNA polymerase III antibody have increased risk for the diffuse cutaneous involvement, hypertensive kidney disease, and poor prognosis.
A positive result for RNA polymerase III antibody may support a diagnosis of systemic sclerosis (SSc) in the appropriate clinical context (see Cautions). Anti-RNA polymerase III autoantibody in patients with SSc is associated with the diffuse cutaneous form of disease and an increased risk of sclerodermal renal crisis.
A negative result indicates no detectable IgG antibodies to RNA polymerase III and does not rule out a diagnosis. The RNA polymerase III IgG ELISA tests only for the RP155 dominant epitope, other epitopes in the antigenic complex are absent and cannot be detected. The overall pooled prevalence of anti-RNAP polymerase III antibody is reported to be 11%, 95% confidence interval: 8 to 14, range of 0 to 41% in published studies.