IMMUNE RESPONSE TO NUCLEAR CONSTITUENTS IN SLE

最近，我们描述了9个不同的核糖核蛋白(RNP)亚集 常成为患者免疫反应靶点的真核细胞 伴有系统性红斑狼疮(SLE)和其他结缔组织 疾病。患者对这些RNPs的抗体是选择性地发生的，并且每个 抗体在免疫沉淀能力上具有极高的特异性。 单个RNP子集。我们假设这些抗体是通过 一种特定的“自动免疫”过程。 我们现在计划扩大我们的观察范围，以包括针对 脱氧核糖核蛋白(DNP)的成分。与我们的 早期的研究，这项工作将提供一个全面的图景 核蛋白(RNPs和DNPs)抗体的总谱 与临床和其他实验室数据进行比较。 这些研究将利用新开发的基于免疫印迹的分析方法。 (蛋白质抗原分析)和DNA-RNA杂交(用于检测 RNA组分)。我们将确定所有的核蛋白决定因素 频繁参与系统性红斑狼疮自身免疫的 系统性红斑狼疮与药物诱导的系统性红斑狼疮和EB的自身免疫反应 病毒感染。一旦确定了准确的目标，我们将 对它们的结构和生化特征进行表征，并确定它们是否 参与形成循环免疫复合体。最基本的 水平，我们的研究将提供有关染色质结构的新信息。 在临床水平上，他们将确定核蛋白抗原是否 可能在系统性红斑狼疮中启动和传播自身免疫反应。 确定诱发疾病的机制(S) 抗核抗体(ANA)可能有助于了解 系统性红斑狼疮的病因。

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.