A peptide DNA surrogate that binds and inhibits anti-dsDNA antibodies

Autoantibodies to dsDNA are an important diagnostic marker and pathogenic factor for systemic lupus erythematosus (SLE). Although the anti-dsDNA antibodies present in SLE are indicative of an antigen-driven response, the antigen has not been conclusively identified. The specific SLE anti-dsDNA antibodies were obtained by affinity purification using a dsDNA-coupled Sepharose column. Using the anti-dsDNA antibodies to screen a phage peptide display library, we demonstrated that purified polyclonal anti-dsDNA antibodies and a monoclonal anti-dsDNA antibody specifically bind a 15 mer peptide ASPVTARVLWKASHV. This chemically synthesized peptide could be recognized by anti-dsDNA antibodies in ELISA and Dot blot. This 15 mer peptide can inhibit anti-dsDNA antibodies binding to dsDNA antigen in immunoassays and in the Crithidia luciliae assay while a control peptide did not inhibit anti-dsDNA antibodies. This study demonstrates the potential usefulness of the peptide DNA surrogate in diagnostic tests of SLE and in the investigation of the origin of anti-dsDNA antibodies. It may also be used in studies of the DNA-anti-DNA antibody interaction.