The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.

The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.
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DOI:
10.1371/journal.pone.0040862
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Pisetsky DS
Pisetsky DS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Stearns NA;Lee J;Leong KW;Sullenger BA;Pisetsky DS

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抗DNA抗体(anti-DNA)是系统性红斑狼疮(SLE)的血清学标志,可通过形成免疫复合物介导疾病的发病机制。由于阻断免疫复合物的形成可以减轻疾病表现,因此研究了核酸结合聚合物(NABP)对体外抗DNA结合的影响。测试的化合物包括聚酰胺胺树状聚合物、1,4-二氨基丁烷核、第3.0代(PAMAM-G3)、溴化己二甲胺和含β-环糊精的聚阳离子。如来自SLE患者的血浆所示,NABP可以在ELISA测定中抑制抗DNA抗体结合。这种抑制是特异性的,因为NABP不影响与破伤风类毒素或Sm蛋白(另一种狼疮自身抗原)的结合。此外,聚合物可以从预先形成的复合物中置换抗体。总之,这些结果表明NABP可以抑制免疫复合物的形成,并可能代表一种新的治疗方法。
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.
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