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  • Review Article
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Anti-DNA antibodies — quintessential biomarkers of SLE

Nature Reviews Rheumatology volume 12, pages 102–110 (2016)Cite this article

Subjects

Key Points

  • Antibodies that recognize DNA (anti-DNA antibodies) can bind to sites on the phosphodiester backbone of single-stranded DNA and double-stranded DNA, to nucleotide sequences or to higher-order structures such as nucleosomes

  • The molecular properties of anti-DNA antibodies, as well as the associated genetic properties, including variable-region somatic mutations, point to a role for antigen selection in anti-DNA antibody generation

  • In the absence of a 'gold standard', various assay formats exist for anti-DNA antibody testing, differing in the nature of DNA substrates and the conditions for binding and detection of antibodies

  • High-affinity binding by an anti-DNA antibody depends on monogamous bivalency, in which both Fab sites of an IgG molecule contact the same polynucleotide chain

  • The use of anti-DNA antibody testing as a measure of disease activity to determine clinical trial eligibility depends on clear understanding of assay differences and the role of anti-DNA antibodies in pathogenesis

Abstract

Antibodies that recognize and bind to DNA (anti-DNA antibodies) are serological hallmarks of systemic lupus erythematosus (SLE) and key markers for diagnosis and disease activity. In addition to common use in the clinic, anti-DNA antibody testing now also determines eligibility for clinical trials, raising important questions about the nature of the antibody–antigen interaction. At present, no 'gold standard' for serological assessment exists, and anti-DNA antibody binding can be measured with a variety of assay formats, which differ in the nature of the DNA substrates and in the conditions for binding and detection of antibodies. A mechanism called monogamous bivalency — in which high avidity results from simultaneous interaction of IgG Fab sites with a single polynucleotide chain — determines anti-DNA antibody binding; this mechanism might affect antibody detection in different assay formats. Although anti-DNA antibodies can promote pathogenesis by depositing in the kidney or driving cytokine production, they are not all alike, pathologically, and anti-DNA antibody expression does not necessarily correlate with active disease. Levels of anti-DNA antibodies in patients with SLE can vary over time, distinguishing anti-DNA antibodies from other pathogenic antinuclear antibodies. Elucidation of the binding specificities and the pathogenic roles of anti-DNA antibodies in SLE should enable improvements in the design of informative assays for both clinical and research purposes.

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Figure 1: The release of DNA from dead and dying cells.
Figure 2: The relationship between IgG antibodies and double-stranded DNA.
Figure 3: The induction of anti-DNA antibodies by bacterial DNA.
Figure 4: Antinuclear antibodies and disease activity in SLE.

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  1. Medical Research Service, Durham Veterans Administration Medical Center, Box 151G, 508 Fulton Street, Durham, 27705, North Carolina, USA

    David S. Pisetsky

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Pisetsky, D. Anti-DNA antibodies — quintessential biomarkers of SLE. Nat Rev Rheumatol 12, 102–110 (2016). https://doi.org/10.1038/nrrheum.2015.151

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