Preferential recognition of peroxynitrite damaged thymidine-monophosphate by anti-DNA autoantibodies in systemic lupus erythematosus

Abstract

This study was undertaken to investigate the role of peroxynitrite (ONOO(-)) modified thymine-5'-monophosphate (TMP) in the generation of anti-DNA autoantibodies in patients with systemic lupus erythematosus (SLE). TMP was exposed to ONOO(-) in vitro and challenged in vivo. TMP and ONOO(-)-modified-TMP were found to be nonimmunogenic in rabbits. TMP-linked-BSA and ONOO(-)-modified-TMP-BSA induced high titer antibodies. Induced antibodies against ONOO(-)-TMP-BSA show crossreactions with nucleic acids conformers. A high degree of specific binding by SLE autoantibodies with ONOO(-)-TMP-BSA was observed. Our novel results provide an important insight into the immunological basis of anti-DNA autoantibodies generation in SLE.