Clinical Information

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.(1,2) 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.(2) 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.(1-3) 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.(3) 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.(1-3)

The human nuclei consist of three RNA polymerases, RNA polymerase I, II and III.(4) 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.(5)

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.(4) This variability may be due to environmental and genetic factors as well as lack of harmonization of immunoassays for the detection of antibodies.(4,6) Positivity for anti-RNA polymerase III antibody is generally mutually exclusive of other SSc-specific antibodies such as centromere and Scl 70.(1-3) In addition, SSc patients who test positive for anti-RNA polymerase III antibodies have increased risk for the diffuse cutaneous involvement, hypertensive kidney disease, and poor prognosis.(1,2)