OLIGONUCLEOTIDES THAT BIND SLE ANTI-DNA ANTIBODIES

虽然系统性红斑狼疮(SLE)的病因尚不清楚，但 抗DNA抗体在系统性红斑狼疮进展中的作用已被认识 三十多年来。识别的DNA上的特定决定因素 致病性抗DNA抗体仍有待阐明。很难做到 识别这些因素源于SLE中抗体的异质性 避免了患者和所需实验的技术挑战。工作 其他人使用抗独特型抗体对抗DNA抗体 这表明尽管有这种异质性，少量的结合位点 对系统性红斑狼疮的病理负责。使用随机方法的最新进展 识别特定识别的寡核苷酸选择策略 蛋白质的元素暗示了致病问题的解决方案 抗DNA抗体决定簇鉴定。使用免疫球蛋白的初步工作 从狼疮小鼠(BXSB)来看，随机选择是合适的 用于鉴定抗DNA抗体决定簇。使用纯化的免疫球蛋白从 系统性红斑狼疮合并肾炎患者，我们建议确定主要DNA序列 致病性抗DNA抗体的特异性决定簇并确定 这些决定因素在SLE患者中的反应性。最终， 被患者免疫球蛋白广泛认可的决定因素将被用作 引导化合物设计阻止破坏免疫形成的药物 并抑制SLE患者致病抗体的产生。

While the cause of systemic lupus erythematosus (SLE) remains unknown, the role of anti-DNA antibodies in the progression of SLE has been recognized for over three decades. Specific determinants on DNA recognized by pathogenic anti-DNA antibodies remain to be elucidated. Difficulty in identifying these elements stems from antibody heterogeneity in SLE patients and from the technical challenges of required experiments. Work by others using anti-idiotypic antibodies against anti-DNA antibodies suggests that despite this heterogeneity a small number of combining sites is responsible for SLE pathology. Recent advances using random oligonucleotide selection strategies to identify specific recognition elements for proteins suggest a solution to the problem of pathogenic anti-DNA antibody determinant identification. Preliminary work using IgG from a lupus mouse (BXSB) indicates that random selection is appropriate for identifying anti-DNA antibody determinants. Using purified IgG from SLE patients with nephritis, we propose to identify the major DNA sequence determinants specific for pathogenic anti-DNA antibodies and to ascertain the reactivity of these determinants among SLE patients. Ultimately, determinants that are widely recognized by patient IgGs will be used as lead compounds to design drugs that block formation of damaging immune complexes and inhibit production of pathogenic antibodies in SLE patients.