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

• Published in: International journal of molecular sciences Vol. 25; no. 5; p. 2556
• Main Authors: Pisetsky, David S., Gedye, Matthew J., David, Lawrence A., Spencer, Diane M.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.02.2024; MDPI
• Subjects: Animals; Antibodies; Antibodies, Antinuclear; Biofilms; Disease; DNA; DNA, Z-Form; E coli; Enzyme-linked immunosorbent assay; Genetic research; Healthy Volunteers; Humans; Immunoglobulin A; Immunoglobulin G; Surface active agents; Urea; isotype; anti-DNA; DNA; antinuclear antibodies; antibodies; conformation; B-DNA; antigen; Z-DNA; biofilms
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25052556

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.