IMMUNOGENICITY OF DNA DAMAGED BY REACTIVE OXYGEN SPECIES - IMPLICATIONS FOR ANTI-DNA ANTIBODIES IN LUPUS

Reactive oxygen species (ROS) are implicated in the inflammatory, auto immune, connective tissue disease, systemic lupus erythematosus (SLE), particularly in respect of processes leading to the formation of path ological anti-DNA antibodies. Exposure to RO increases the antigenicit y of DNA for SLE antibodies, but data on the immunogenicity of ROS-DNA are not conclusive. In this study, we have examined the immunogenicit y in rabbits, of DNA modified by three hydroxyl radical generating sys tems. Additionally, we investigated the antigenicity of UVA, WE, and U VC irradiated DNA for lupus anti-DNA antibodies. Modification of DNA b y both ROS and far UV dramatically increased its immunogenicity; the F e2+ and H2O2 system resulted in antibodies that recognized both native and modified DNA. In our ELISA system, none of the UV antigens showed any antigenicity above native DNA for SLE sera. The data suggested th at different profiles of antigenicity and immunogenicity arise depende nt on the method of ROS production, but also that ROS-DNA may be a fac tor in antigen-driven immune complex formation in SLE. Copyright (C) 1 996 Elsevier Science Inc.