Anti–Scl-70 Antibodies

SARDs are a heterogeneous group of disorders characterized by dysregulation of the immune system, that starts to turn against the body’s own tissues. Major SARDs include systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and Sjögren’s syndrome. These diseases can affect multiple organs and share common symptoms such as fatigue, fever, joint pain and skin rash. Diagnosis relies on a combination of clinical assessment and specific autoantibody tests. Early diagnosis is crucial to initiate appropriate therapy and slow down disease progression.

The Scl-70 antigen was first described in 1979 as a ~70 kDa nuclear protein associated with chromatin. Subsequent studies identified the antigenic target of these autoantibodies as topoisomerase I (Topo I), a nuclear enzyme involved in resolving DNA supercoiling during replication and transcription.

Anti-Scl-70 (anti-topoisomerase I) antibodies are considered highly specific for systemic sclerosis (SSc), particularly the diffuse cutaneous subtype (dcSSc). Their presence is exceedingly rare in healthy individuals or in other systemic connective tissue diseases, making them useful in the differential diagnosis from other SARDs.

Because of their diagnostic value, they are included in the 2013 ACR/EULAR classification criteria for systemic sclerosis. Beyond classification, anti-Scl-70 antibodies carry important prognostic information: their presence is associated with a higher risk of interstitial lung disease (ILD) – which may occur in up to 50% of seropositive patients – and with increased mortality, especially in the early years after diagnosis.