The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.
Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE) and can mediate disease pathogenesis by the formation of immune complexes. Since blocking immune complex formation can attenuate disease manifestations, the effects of nucleic acid binding polymers (NABPs) on anti-DNA binding in vitro were investigated. The compounds tested included polyamidoamine dendrimer, 1,4-diaminobutane core, generation 3.0 (PAMAM-G3), hexadimethrine bromide, and a β-cylodextrin-containing polycation. As shown with plasma from patients with SLE, NABPs can inhibit anti-DNA antibody binding in ELISA assays. The inhibition was specific since the NABPs did not affect binding to tetanus toxoid or the Sm protein, another lupus autoantigen. Furthermore, the polymers could displace antibody from preformed complexes. Together, these results indicate that NABPs can inhibit the formation of immune complexes and may represent a new approach to treatment.
Duke University Medical Center, Department of Medicine, Durham, North Carolina, United States of America.
Nancy A
NA
Stearns
Jaewoo
J
Lee
Kam W
KW
Leong
Bruce A
BA
Sullenger
David S
DS
Pisetsky
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology; D019921:Biotinylation / Q000187:drug effects; D004247:DNA / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D011108:Polymers / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013744:Tetanus Toxin / Q000276:immunology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000941:Antigens; D011108:Polymers; D013744:Tetanus Toxin; D004247:DNA