Systemic sclerosis is a multisystem connective tissue (systemic rheumatic) disease characterized by fibroblast dysfunction leading to fibrosis of the skin and internal organs, microvascular injury leading to tissue hypoxia, and an autoimmune response manifested by production of autoantibodies. The severity of the disease is highly variable among individual patients. Limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis have been recognized as distinct subsets, with worse survival for those with the diffuse form. Clinical features of CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) can be seen in both limited cutaneous and diffuse cutaneous forms but, overall, are associated with a better prognosis. Several disease-specific and mutually exclusive autoantibodies have been identified that are helpful in both diagnosis and disease classification. Centromere and topoisomerase I (Scl 70) autoantibodies are associated with limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis, respectively.
 
RNA polymerase III is a complex, 16-subunit enzyme directing transcription of small, stable nontranslated RNA genes: tRNA, 5S rRNA, Alu RNA, U6 snRNA, and 7SK snRNA genes. The immunodominant epitope for autoantibodies with anti-RNA polymerase I/III specificity has been identified on the RNA polymerase-specific subunit RPC155.
 
Autoantibodies to RNA polymerase III antigen are found in 11% to 23% of patients with systemic sclerosis. Systemic sclerosis patients who are positive for RNA polymerase III antibodies form a distinct serologic subgroup and usually do not have any of the other antibodies typically found in systemic sclerosis patients such as anticentromere or anti-Scl70. Numerous studies have shown that systemic sclerosis patients with anti-RNA polymerase III have an increased risk of the diffuse cutaneous form of scleroderma, with a high likelihood of skin involvement and hypertensive renal disease.
 

A positive result supports a possible diagnosis of systemic sclerosis (see Cautions). This autoantibody is strongly associated with diffuse cutaneous scleroderma and with an increased risk of acute renal crisis. 
 
A negative result indicates no detectable IgG antibodies to RNA polymerase III, but does not rule out the possibility of systemic sclerosis (11%-23% sensitivity).