Introduction: In the present study, the detection of anti-topoisomerase I (anti-topo I) autoantibodies was evaluated for diagnosis and risk assessment of systemic sclerosis (SSc) patients in a well characterized large monocentric cohort.
Methods: Sera from patients with SSc (diffuse n = 96, limited n = 113), from patients with overlap syndromes (n = 51), from patients with other diseases associated with SSc (n = 20), as well as from disease controls (n = 487) were analysed for the presence of anti-topo I antibodies by line immunoblot assay and ELISA. Assessment of organ manifestations was performed as proposed by the European Scleroderma Trial and Research network.
Results: The applied test systems for the detection of anti-topo I antibodies revealed a diagnostic sensitivity for SSc of approximately 24% and a diagnostic specificity of at least 99.6%. The sensitivity to identify patients with diffuse SSc amounted to 60%. Patients with anti-topo I antibodies showed a higher burden of skin and lung fibrosis, contractures, electrocardiogram changes, as well as digital ulcers and had more active disease than antibody-negative patients. Signal strengths correlated only weakly with disease activity, with modified Rodnan skin score, with predicted forced vital capacity, and with predicted diffusion capacity levels (P = 0.01, rho = 0.234, rho = 0.413, rho = -0.215, rho = -0.219). High signal intensities were associated with an increased mortality in diffuse SSc patients (P = 0.003).
Conclusions: Diagnosis and risk assessment of SSc patients can be supported by the detection of anti-topo I antibodies. Signal intensities as obtained by line immunoblot assay or ELISA can be used as a surrogate marker for fibrosis, active disease and worse prognosis.