Antibodies that bind to an EBV derived peptide mimic of dsDNA, have pathogenic potential

Abstract

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of antibodies to double stranded DNA (dsDNA) that can deposit in the kidney leading to nephritis. Our laboratory has previously been studying the association of SLE with the Epstein Barr Virus (EBV). We generated two monoclonal antibodies designated 3D4 and 16D2, that bind to a peptide (PFM-15) in the carboxyl region of a major nuclear protein of EBV (EBNA-1) and cross-react with dsDNA. In the present study, we demonstrate that both of these monoclonal antibodies can bind to fixed preparations of rat glomeruli suggesting pathogenic potential. Immunostaining is dramatically reduced when glomeruli are pre-treated with DNase indicating that these antibodies recognize chromatin associated structures. In addition, the PFM-15 peptide inhibits 3D4 and 16D2 from binding to glomeruli and inhibits both antibodies from binding to dsDNA coated plates by ELISA. This suggests that PFM-15 can act as a molecular mimic of dsDNA. Our results demonstrate that antibodies that recognize a viral peptide and cross-react with dsDNA can bind to glomeruli and therefore have pathogenic potential. This study further supports an association between EBV and SLE and supports the role of molecular mimicry in autoimmune disease.