Clinical Information

Scl 70 (DNA topoisomerase 1) is an enzyme localized in both the cytoplasm and the nucleoli of the interphase cell that is an autoantibody target in patients with systemic sclerosis (SSc).(1,2) SSc is a complex autoimmune rheumatic disease of unknown etiology, characterized by widespread vasculopathy, fibrosis of the skin and internal organs, and immunologic derangements, including the production of diverse autoantibodies.(3-5) Antibody to Scl 70 is considered specific for SSc (also referred to as scleroderma) and together with anti-centromere and anti-RNA polymerase III autoantibodies is recommended for the diagnostic classification for disease by the American College of rheumatology/European League Against Rheumatism collaborative initiative.(3) Antibody to Scl 70 is typically associated with diffuse cutaneous SSc (dcSSc), a clinical subset of SSc which is characterized by disease severity including musculoskeletal and cardiac involvement, interstitial lung disease and poor survival outcomes.(4,5) In addition, Scl 70 antibody are more commonly found in African American patients with dcSSc compared to their Caucasian counterpart.(6,7)

In general, the presence of Scl 70 antibody is associated with a positive antinuclear antibody (ANA) when tested with the HEp-2 substrate using the indirect immunofluorescence assay (IFA).(1,2) ANA positivity with HEp-2 substrate IFA referred to as Scl-70 pattern is a composite of five cellular regions: nucleus, nucleolus and cytoplasm in interphase cells; nucleolar organizing region and chromosomes in mitotic cells.(2) Antibodies to Scl 70 were traditionally tested in clinical laboratories using immunodiffusion (ID), however, with increasing demands, methods for the detection and quantification of these autoantibodies have evolved to include diverse types of solid-phase immunoassays (SPAs) such as the line immunoblot, enzyme-linked immunosorbent assay, multiplex bead immunoassay, chemiluminescence immunoassay, and fluorescence enzyme immunoassay.(6-10) These SPAs have been reported to be less specific than the ID, especially in distinguishing SSc patients from those with other rheumatic diseases, though performance characteristics of individual assays may vary.(6-8). In a recent report, it was noted that discrepancy between anti-Scl-70 antibody assays can have relevant implications for clinical care and trial enrichment strategies for SSc patients with interstitial lung disease.(9)

Data from routine clinical practice do suggest that at diagnosis, positive results for Scl 70 antibody using SPAs must be interpreted in the appropriate clinical context taking into consideration the presence of a positive ANA test using the HEp-2 substrate by IFA, and/or the level of anti-Scl 70 antibody level.(6-8, 10) Low levels of anti-Scl 70 antibodies have been reported in non-SSc patients including those with SLE.(6, 8, 10) In SLE patients, it remains to be determined if this points to a unique subset of individuals or the phenomenon is due to cross-reactivity with dsDNA antibody.(10) Based on this observation, testing for dsDNA antibody may provide additional diagnostic clues, especially in the absence of the ID assay.(10)

For more information see Connective Tissue Disease Cascade.