Diagnostic value of anti-topoisomerase I antibodies in a large monocentric cohort
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* Corresponding author: Gabriela Riemekasten gabriela.riemekasten@charite.de
1 Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany
2 EUROIMMUN Medizinische Labordiagnostika AG, Seekamp 31, Lübeck 23560, Germany
3 German Rheumatism Research Centre, Charitéplatz 1, Berlin 10117, Germany
Arthritis Research & Therapy 2009, 11:R28 doi:10.1186/ar2622
Published: 21 February 2009Abstract
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, ρ = 0.234, ρ = 0.413, ρ = -0.215, ρ = -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.