IMMUNE RESPONSE TO NUCLEAR CONSTITUENTS IN SLE

我们的长期目标是了解系统性狼疮的病因 红斑性狼疮（SLE）。 我们目前的工作力求提供一个全面的 不同抗原抗体系统的图片， 核糖核蛋白在这种疾病的患者。 结果是， 发展的假设，特定的核蛋白，特别是 U1 snRNP，核小体和Ro颗粒，积极地引发并可能 会传播自身免疫反应 为了发展这个假设 此外，我们现正集中力量研究架构， 新发现的自身抗原Ku蛋白的生物学功能 我们假设染色质成分在DNA修复中起作用， 转座--和Ro颗粒--这是自身免疫性疾病的中心焦点 SLE患者的反应。 对Ku蛋白的研究将寻求建立其结构和生物学特性。 功能 我们将使用克隆和标准的生物化学方法， 表征该蛋白的结构并鉴定其自身抗原性 表位 此外，我们还将使用 各种生物测定系统。 最后，我们将开发一种新的ELISA 用于在使用重组蛋白的临床研究中测量抗Ku抗体 Ku蛋白作为抗原。 Ro粒子的研究工作将集中在开发特定的 探针--包括单克隆抗体--可以识别它， 在体外重建它的方法，以及确定它在 细胞 此外，我们将比较患者血清和免疫动物血清 血清中的特定Ro蛋白表位识别。 这项工作将提供有关Ku结构的新信息 蛋白质和Ro粒子。 它可能成功地定义了生物学 这些新发现的细胞因子的功能。 信息 Ku蛋白和Ro颗粒的结构和功能可能有所帮助 我们理解了为什么某些核蛋白会成为选择的靶点。 SLE患者的自身免疫反应。

Our long-range objective is to understand the etiology of systemic lupus erythematosus(SLE). Our present work has sought to provide a comprehensive picture of the different antigen-antibody systems that involve ribonucleoproteins in patients with this disease. The outcome has been the development of the hypothesis that specific nucleoproteins, especially the U1 snRNP, the nucleosome, and the Ro particle, actively elicit and possibly propagate autoimmune responses in this disease. To develop this hypothesis further, we are now concentrating our efforts to study the structure and biologic function of the autoantigenic Ku protein--a newly discovered chromatin component which we hypothesize plays a role in DNA repair or transposition--and the Ro particle--which is a central focus of autoimmune responses in patients with SLE. Work on the Ku protein will seek to establish its structure and biologic function. We will use cloning and standard biochemical approaches to characterize this protein structurally and to identify its autoantigenic epitopes. In addition, we will seek to identify its function using a variety of biological assay systems. Finally we will develop a new ELISA for measurement of anti-Ku antibodies in clinical studies using recombinant Ku protein as antigen. Work on the Ro particle will concentrate on developing specific probes--including monoclonal antibodies--that recognize it, devising a method for reconstituting it in vitro, and determining its location in cells. In addition, we will compare patient sera with immunized animal sera in terms of specific Ro protein epitopes recognized by each. This work will provide new information about the structure of the Ku protein and the Ro particle. It may succeed in defining the biological function of these newly recognized cellular elements. Information about the structure and function of the Ku protein and the Ro particle could help us understand why certain nucleoproteins become targets for selected autoimmune responses in patients with SLE.