Standardized detection of anti-ds DNA antibodies by indirect immunofluorescence - a new age for confirmatory tests in SLE diagnostics.

摘要

We read with great interest the well conducted comparative study of different techniques for the detection of antibodies to double-stranded (ds) DNA by Chiaro et al. in this journal recently [1]. The authors concluded that the Crithidia luciliae immunofluorescence test (CLIFT) is still a relevant confirmatory tool comparing it with 6 different enzyme immunoassays (EIAs). However, their data demonstrated significant differences in the analytical concordance between ELISAs for detecting anti-dsDNA IgG antibodies and the CLIFT confirmatory with implications for interlaboratory testing. Until recently, a moderate sensitivity of anti-dsDNA antibody detection by CLIFT was usually reported regarding the diagnosis of systemic lupus erythematosus (SLE) [2]. An improved sensitivity of anti-dsDNA IgG results by a novel CLIFT employing the kinetoplast DNA of the hemoflagellate C. luciliae as a solid-phase autoantigen with a changed reaction environment was reported by our group recently [3,4]. As a fact, this modified CLIFT showed an increased sensitivity of 76.4% with a high specificity of 99% characteristic for commercial CLIFT assays in general. The novel CLIFT was characterized by a better correlation with Farr assay rather than with ELISA results. Thus, the relatively low specificity of just 84% for the CLIFT assay reported by Chiaro et al. in their study is remarkably surprising. It is well accepted that CLIFT anti-dsDNA results are highly appreciated by clinicians due to the unsurpassed high specificity of this parameter in particular for clinical complications like lupus nephritis. Antibodies against dsDNA are known to be highly heterogeneous with respect to their epitope specificity, avidity, immunoglobulin subclass composition, and complement-fixing avidity. However, the real autoantigenic target structure for anti-dsDNA IgG antibodies in patients with SLE has not been identified yet and consequently the diagnostic performance of anti-dsDNA antibody testing varies ...