Sensitivity and Specificity of Immunological Methods for the Detection of Anti-Topoisomerase I (Scl70) Autoantibodies: Results of a Multicenter Study (Clinical Immunology‪)‬

The anti-topoisomerase I antibodies (anti-topo I and anti-Scl70) are serological markers of diffuse systemic sclerosis (1) and among its fundamental diagnostic-classification criteria (2, 3). This rare but serious disease also involves very high social and economic costs (4), and the contribution of the autoimmunology laboratory to its diagnosis is essential, thus requiring very high quality analysis. Studies conducted by other workers and our group (5-12) that addressed the reliability of the immunometric methods in identifying anti-Scl70 antibodies have furnished discordant results, with very variable sensitivities and specificities. Indeed, this phenomenon was confirmed by a recent cooperative study (13) that evidenced remarkable differences in sensitivity (range, 20-100%) and specificity (range, 85-100%) although CDC/WHO referral sera were used (14). Moreover, in addition to the differences in the designs of the above studies, the variations encountered might also be explained by the diverse characteristics and numbers of the patients examined as well as differences in the type of laboratory involved and the reagents used. In addition, most of these studies involved selected reference laboratories that used home-made methods, whereas most clinical laboratories use only commercial reagents. In recent years, the use of antigenic substrates obtained with molecular biology techniques and the optimization of methods for the extraction and purification of native antigens have contributed to a more precise characterization and identification of these and other autoantibodies indicative of autoimmune diseases. Moreover, the continuous development of analytical techniques has made possible the use of new commercial tests for the determination of the various autoantibody specificities in an ever increasing number of laboratories, thus requiring continuous verification of quality. For this reason, the Study Group on the Diagnosis of Autoimmune Diseases of the Italian Society of Laboratory Medicine has performed an extensive multicenter study involving hospital clinical laboratories to analyze serum samples from patients affected by systemic sclerosis, using numerous commercial methods and reagent set to define present-day reliability in determining anti-topoisomerase I autoantibodies.