IMMUNE RESPONSE TO NUCLEAR CONSTITUENTS IN SLE

最近，我们描述了9种不同的核糖核蛋白（RNP）亚型， 真核细胞经常成为患者免疫反应的目标， 系统性红斑狼疮（SLE）和其他结缔组织 疾病 患者对这些RNP的抗体选择性地发生，并且每种抗体都是 抗体在其免疫沉淀能力方面是非常特异的 单个RNP子集。 我们假设这些抗体是通过 一种特殊的“自身免疫”过程。 我们现在计划将我们的观察扩展到包括针对 脱氧核糖核蛋白（DNP）。 结合我们 早期的研究，这项工作将提供一个全面的图片， 核蛋白（RNP和DNP）抗体的总谱 与临床和其他实验室数据进行比较。 这些研究将利用基于免疫印迹的新开发的测定法 (for蛋白抗原分析）和DNA-RNA杂交（用于检测 的RNA）。 我们将确定所有的核蛋白决定簇 经常参与SLE自身免疫，并比较 系统性红斑狼疮与药物诱导的系统性红斑狼疮和EB病毒的自身免疫反应 病毒感染。 一旦确定了准确的目标，我们将 从结构上和生物化学上对它们进行表征，并确定它们是否 参与循环免疫复合物的形成。 在一个基本 在水平上，我们的研究将为染色质结构提供新的信息。 在临床水平上，他们将确定核蛋白抗原是否是 可能引发和传播SLE的自身免疫反应。 确定负责引入《公约》的机制 抗核抗体（ANA）可能会提供对 SLE的病因。

Recently, we described 9 different ribonucleoprotein (RNP) subsets within eukaryotic cells that often become targets for immune responses in patients with systemic lupus erythematosus (SLE) and other connective tissue diseases. Patient antibodies to these RNPs occurred selectively, and each antibody was exquisitely specific in its ability to immunoprecipitate individual RNP subsets. We hypothesize that these antibodies arise through a specific process of "autoimmunization". We now plan to extend our observations to include antibodies directed at components of deoxyribonucleoprotein (DNP). In combination with our earlier studies, this work will provide a comprehensive picture of the total spectrum of antibodies to nucleoproteins (both RNPs and DNPs) for comparison with clinical and other laboratory data. These studies will utilize newly developed assays based on immunoblotting (for analysis of protein antigens) and DNA-RNA hybridization (For detection of RNA components). We will identify all of the nucleoprotein determinants that participate frequently in the autoimmunity of SLE and compare the autoimmune responses of SLE with those of drug-induced SLE and Epstein-Barr virus infection. Once the precise targets are identified, we will characterize them structurally and biochemically and determine if they participate in the formation of circulating immune complexes. At a basic level, our studies will provide new information about chromatin structure. At a clincal level, they will determine whether nucleoprotein antigens are likely to initiate and propagate autoimmune responses in SLE. Identification of the mechanism(s) responsible for the induction of antinuclear antibodies (ANAs) is likely to provide an understanding of the etiology of SLE.