antitopoisomerase

Antitopoisomerase antibodies are autoantibodies directed against human DNA topoisomerases, enzymes that regulate DNA topology during replication and transcription. The most clinically relevant are antibodies to topoisomerase I (Topo I) and to topoisomerase II (Topo II).

Anti-topoisomerase I antibodies (often called anti–Topo I or anti–Scl-70) are the best characterized. They are strongly associated with diffuse cutaneous systemic sclerosis (dcSSc) and with an elevated risk of interstitial lung disease. Their presence supports the diagnosis of systemic sclerosis and helps predict disease subset and prognosis, though they are not disease-specific and may be found in other connective tissue diseases in lower frequencies.

Antibodies to topoisomerase II isoforms (Topo IIα and Topo IIβ) are less disease-specific. They have been reported in a minority of patients with systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune conditions; they are not routinely used to confirm a particular diagnosis. In oncology contexts, topo II–targeting agents like etoposide interact with the enzyme, but this pharmacologic relationship is separate from autoimmune antibodies.

Clinical testing employs serologic assays such as ELISA or immunoblotting, typically alongside screening for other myositis or connective tissue disease antibodies. The detection of anti–Topo I antibodies can inform risk assessment in systemic sclerosis but must be interpreted in the full clinical context.

In summary, antitopoisomerase antibodies constitute an important autoimmune serologic group, strongest in relation to systemic sclerosis, and reflect the broader role of topo enzymes as immune targets.