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.

Keywords:

• Anti-DNA autoantibodies
• thymine monophosphate
• systemic lupus erythematosus
• autoimmunity
• peroxynitrite

Acknowledgments

This work was fully supported by grant SR-D-011-952 awarded by the Research Deanship, Qassim University. Authors also thank Professor Abdullah Alghasham (Dean, College of Medicine) for providing research facilities. Maintenance of experimental animals during the whole study by Dr. Syed El-Deep Mahana (Veterinarian) is gratefully acknowledged.H.A.A., A.A.R., A.A.A., and M.I.K. carried out the experimental work, data collection, and interpretation. W.I.A.W. and H.A.H. carried out sample collection. Z.R. conceived of the study, its design, experimentation, coordination, data interpretation, and manuscript drafting. All authors have read and approved the final manuscript.The authors declare that they have no conflict of interest.