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Anti-dsDNA Method Discordance — SCE Rheumatology MCQ

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HardAutoimmune SerologyAnti-dsDNA Method DiscordanceSCE Rheumatology

A 45-year-old woman with established systemic lupus erythematosus has the same serum aliquot tested for anti-dsDNA by two laboratories. A conventional solid-phase ELISA is positive at 45 IU/mL according to that laboratory's reference range, whereas a Farr radioimmunoassay is negative. Repeating the ELISA with a chaotropic urea wash reduces the signal below the positive cut-off. Which methodological explanation best accounts for these findings?

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Correct answer: C — Low-avidity DNA–antibody complexes remain detectable by conventional ELISA but are disrupted under the stringent Farr assay conditions

The correct answer is C. Loss of the ELISA signal after a chaotropic urea wash demonstrates low-avidity antibody binding. Conventional solid-phase ELISAs may retain both lower- and higher-avidity anti-dsDNA, whereas the high-ionic-strength precipitation conditions of the Farr assay disrupt low-avidity DNA–antibody complexes and preferentially detect higher-avidity antibodies. Thus, an ELISA-positive/Farr-negative pattern can occur without laboratory error. The distinction is not simply IgM versus IgG, and the Farr assay uses labelled double-stranded DNA rather than single-stranded DNA or Crithidia substrate. Complement binding and a hook effect do not explain the urea-sensitive ELISA result. Anti-dsDNA values and cut-offs are also method-dependent, so numerical results from different assays should not be treated as directly interchangeable.

Reference: Villalta D et al. Anti-dsDNA antibody avidity determination by a simple reliable ELISA method for SLE diagnosis and monitoring. Lupus. 2003;12:31–36. https://pubmed.ncbi.nlm.nih.gov/12587824/