Autoantibody Signatures as Biomarkers of Interstitial Cystitis.

项目总结/摘要： 间质性膀胱炎（IC）是一种使人衰弱的慢性膀胱综合征。目前，没有经过验证的 IC的生物标志物。然而，炎症与IC相关是公认的。虽然 自身免疫被认为是一个潜在的原因，IC的某些方面表明它可能在以下方面发挥作用： 引发或维持这种疾病中明显的慢性炎症反应。比如说， 在IC患者的血清中检测到的自身抗体的程度大于对照组， IC中自身抗体所识别的抗原种类繁多，提示膀胱退变 上皮细胞的出现可能会刺激自身抗体的产生。因此， IC中的炎症/自身免疫可能允许使用身体自身的免疫应答作为一种手段， 鉴定IC的生物标志物。显然，了解这些潜在的自身抗原可能会更好地使 更深入地了解IC的病理生物学，并促进自身抗体的开发或使用 作为潜在的诊断生物标志物。 尽管自身抗体具有所有潜在的优势，但其致命弱点是它们的敏感性。教训 显示通常只有15-20%的患者表现出对自身免疫性疾病的任何反应。 给定抗原。然而，蛋白质组学可能是成功的关键，因为它能够提供 是指多路复用。通过将对几种抗原的反应联系在一起， 测试的难度大大增加。 最近，我们描述了一种 反向捕获 自身抗体微阵列 使用高密度单克隆抗体捕获阵列固定500种特定抗原的平台。 这些抗原靶标是参与信号转导、细胞周期调节、基因表达和免疫调节的蛋白质。 转录、细胞凋亡、细胞生长、受体、膜蛋白以及粘附和迁移 分子。使用固定化的抗原作为 诱饵， 我们就能确定自身抗体的反应性 测试和对照之间的固定化抗原。 我们相信这个平台可能非常适合IC的研究。因此，我们的研究目标是 这些应用是：1）测试来自患有以下疾病的患者的血清自身抗体库的假设： IC可用于自身抗体谱分析，和2）确定其可行性、稳健性和 的再现性 反向捕获 自身抗体微阵列鉴定自身抗体特征， IC的生物标志物。

PROJECT SUMMARY/ABSTRACT: Interstitial cystitis (IC) is a debilitating, chronic bladder syndrome. Currently, there are no validated biomarkers for IC. It is well established, however, that inflammation is associated with IC. Although autoimmunity is debated as a potential cause, certain aspects of IC suggest that it may play a role in initiating or sustaining the chronic inflammatory response evident in this disease. For example, autoantibodies have been detected in the sera of IC patients to a greater extent than in controls, and the variety of antigens recognized by autoantibodies in IC suggests that the degeneration of bladder epithelial cells that occurs may stimulate the production of autoantibodies. Thus, the presence of inflammation/autoimmunity in IC may allow the use of the body's own immune response as a means of identifying biomarkers of IC. Clearly, knowledge of these potential autoantigens might better enable a greater understanding of the pathobiology of IC, and facilitate the development or use of autoantibody signatures as potential diagnostic biomarkers. With all of the potential advantages, the Achilles heel of autoantibodies is their sensitivity. Lessons from autoimmune diseases show that typically only 15-20% of patients demonstrate a response to any given antigen. However, proteomics may hold the key to success because of its ability to provide the means to multiplex. By linking the responses to several antigens together, the sensitivity and specificity of the test increases considerably. Recently, we described the development and use of a reverse capture autoantibody microarray, a platform that immobilizes 500 specific antigens using a high-density monoclonal antibody capture array. These antigen targets are proteins that are involved in signal transduction, cell-cycle regulation, gene transcription, apoptosis, cell growth, receptors, membrane proteins, as well as adhesion and migration molecules. Using the immobilized antigens as baits, we can determine the autoantibody reactivity between test and controls to the immobilized antigens. We believe this platform may be well suited for the study of IC. Thus, the objectives of our research for this application are: 1) to test the hypothesis that the serum autoantibody repertoire from patients with IC can be exploited for autoantibody profiling, and 2) to determine the feasibility, robustness, and reproducibility of the reverse capture autoantibody microarray to identify autoantibody signatures as biomarkers of IC.