The Binding Properties of Antibodies to Z-DNA in the Sera of Normal Healthy Subjects

Int J Mol Sci. 2024 Feb 22;25(5):2556. doi: 10.3390/ijms25052556.

Abstract

Antibodies to DNA are a diverse set of antibodies that bind sites on DNA, a polymeric macromolecule that displays various conformations. In a previous study, we showed that sera of normal healthy subjects (NHS) contain IgG antibodies to Z-DNA, a left-handed helix with a zig-zig backbone. Recent studies have demonstrated the presence of Z-DNA in bacterial biofilms, suggesting a source of this conformation to induce responses. To characterize further antibodies to Z-DNA, we used an ELISA assay with brominated poly(dGdC) as a source of Z-DNA and determined the isotype of these antibodies and their binding properties. Results of these studies indicate that NHS sera contain IgM and IgA as well as IgG anti-Z-DNA antibodies. As shown by the effects of ionic strength in association and dissociation assays, the anti-Z-DNA antibodies bind primarily by electrostatic interactions; this type of binding differs from that of induced anti-Z-DNA antibodies from immunized animals which bind by non-ionic interactions. Furthermore, urea caused dissociation of NHS anti-Z-DNA at molar concentrations much lower than those for the induced antibodies. These studies also showed IgA anti-Z-DNA antibodies in fecal water. Together, these studies demonstrate that antibodies to Z-DNA occur commonly in normal immunity and may arise as a response to Z-DNA of bacterial origin.

Keywords: B-DNA; DNA; Z-DNA; anti-DNA; antibodies; antigen; antinuclear antibodies; biofilms; conformation; isotype.

MeSH terms

  • Animals
  • Antibodies, Antinuclear
  • DNA, Z-Form*
  • Healthy Volunteers
  • Humans
  • Immunoglobulin A
  • Immunoglobulin G

Substances

  • DNA, Z-Form
  • Antibodies, Antinuclear
  • Immunoglobulin G
  • Immunoglobulin A