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Anti-dsDNA Testing Methods — SCE Rheumatology MCQ

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HardAutoimmune SerologyAnti-dsDNA Testing MethodsSCE Rheumatology

A 45-year-old woman undergoing investigation for possible systemic lupus erythematosus has a low-positive anti-dsDNA result on a solid-phase ELISA. Because the result is discordant with the remainder of her serology, the laboratory tests the same sample using a Farr radioimmunoassay. Which analytical feature of the Farr assay provides the principal rationale for this confirmatory approach?

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Correct answer: E — High-salt ammonium sulfate precipitation disrupts low-avidity complexes, selecting relatively high-avidity anti-dsDNA

The correct answer is E. In the Farr assay, radiolabelled dsDNA–antibody complexes are precipitated under high-salt conditions using ammonium sulfate. These conditions dissociate relatively low-avidity complexes, so the retained signal is enriched for high-avidity anti-dsDNA. This historically gave Farr testing high specificity for SLE compared with many conventional solid-phase ELISAs, which may detect a broader avidity spectrum. However, modern immunoassays vary substantially, and an ELISA result is not intrinsically false positive. Option C describes a feature of solid-phase assays rather than Farr testing. Option B describes the Crithidia luciliae immunofluorescence test, which uses kinetoplast DNA. Farr is not an IgM-selective assay, and radiolabelling itself does not preferentially amplify low-avidity binding. Farr results should therefore not be treated as quantitatively interchangeable with other anti-dsDNA methods.

Reference: Smeenk R, van der Lelij G, Aarden L. Avidity of antibodies to dsDNA: comparison of IFT on Crithidia luciliae, Farr assay, and PEG assay. Journal of Immunology. 1982;128:73–78. https://pubmed.ncbi.nlm.nih.gov/20303931/