The integration of the detection of systemic sclerosis-associated antibodies in a routine laboratory setting: comparison of different strategies

Background: Detection of systemic sclerosis-associated autoantibodies (SSc-Ab) is mostly restricted to anticentromere and anti-topoisomerase-I. However, antiRNA-polymerase-III and anti-PM/Scl are also important diagnostic markers for the disease supporting their incorporation in the laboratory repertoire. The aim of this study was to compare different testing strategies integrating the identification of these extra SSc-Ab in a routine testing algorithm. Methods: Sera from 144 consecutive SSc-patients and 265 controls were screened for antinuclear antibodies (ANA) by indirect immunofluorescence (ANA IIF) and tested for anti-extractable nuclear antigen (ENA) using five different assays that differ in their ability to detect SSc-Ab [two screening enzyme immunossays (EIA) with antigen mixtures, one multi-parameter line-immunoassay and two EIA with individual antigens]. Results: The application of SSc-Ab testing in cascade with the routine ANA/anti-ENA tests improved diagnostic performance characteristics. Besides the type of algorithm, also the number of antigens included in the screening EIA as well as the expected patient/control ratio, influenced the average expected costs and the number of additional SSc-Ab tests to be performed. In laboratories with an expected patient/control ratio of 0.002, cascade testing was most exploited by the use of a screening EIA that included all SSc-Ab as a secondary test after ANA IIF. Conclusions: Restriction of the performance of additional SSc-Ab assays based on the results of prior ANA/anti-ENA tests is a cost-effective strategy allowing optimized use of laboratory resources with minimal loss in diagnostic capacity.