Antibodies elicited in response to EBNA-1 may cross-react with dsDNA. (93.29)

Abstract

Several genetic and environmental factors have been linked to Systemic Lupus Erythematosus (SLE). One environmental trigger that has a strong association with SLE is the Epstein Barr Virus (EBV). Our laboratory previously demonstrated that BALB/c mice expressing the EBNA-1 protein, developed antibodies to double stranded DNA (dsDNA). The present study was undertaken to determine the basis for this anti-dsDNA response. We now demonstrate that BALB/c mice immunized with recombinant EBNA-1 protein develop antibodies to EBNA-1 that cross-react with dsDNA. Close examination of two monoclonal antibodies to EBNA-1 has demonstrated their reactivity with dsDNA but not unrelated proteins and absorption on dsDNA cellulose columns removes their reactivity to both dsDNA and EBNA-1. In addition, these monoclonal antibodies recognize different regions of the EBNA-1 protein suggesting that more than one epitope in EBNA-1 may be the target of antibodies that cross-react with dsDNA. These results support the association of SLE with EBV and emphasize the need to prevent EBV infection or to mask EBNA-1 protein from the immune system following EBV exposure, in order to minimize the risk of autoimmunity.