PREFERENTIAL RECOGNITION OF PEROXYNITRITE DAMAGED THYMIDINE-MONOPHOSPHATE BY ANTI-DNA AUTOANTIBODIES IN SYSTEMIC LUPUS ERYTHEMATOSUS

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.