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.
Department of Medical Biochemistry, College of Medicine, Qassim University, Buraidah, Saudi Arabia. zafarrasheed@rocketmail.com
Zafar
Z
Rasheed
Hani A
HA
Al-Shobaili
Ahmad A
AA
Al Robaee
Abdullateef A
AA
Alzolibani
Walid I A
WI
Wadi
Muhammad Ismail
MI
Khan
Hamad A
HA
Al-Hamed
D000293:Adolescent; D000328:Adult; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001667:Binding, Competitive; D016022:Case-Control Studies; D004249:DNA Damage / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D030421:Peroxynitrous Acid / Q000276:immunology*; D011485:Protein Binding; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000276:immunology; D013938:Thymidine Monophosphate / Q000276:immunology*; D055815:Young Adult
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D030421:Peroxynitrous Acid; D012710:Serum Albumin, Bovine; D013938:Thymidine Monophosphate