Autoantibody Signatures as Biomarkers of Interstitial Cystitis.

自身抗体特征作为间质性膀胱炎的生物标志物。

• 批准号: 7290162
• 负责人: BRIAN C.-S. LIU
• 金额: $ 26.25万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7290162
• 关键词: Adhesions; Age; Antibodies; Antigen Targeting; Antigens; Apoptosis; Area; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmune Responses; Autoimmunity; Binding; Biological; Biological Markers; Bladder; Cell Cycle Regulation; Chronic; Clinical; Condition; Coupled; Development; Diagnosis; Diagnostic; Disease; Epithelial Cells; Feasibility Studies; Frequencies; Gender; Genetic Transcription; Goals; Heel; Immune response; Immunoprecipitation; Increased frequency of micturition; Individual; Inflammation; Inflammatory Response; Interstitial Cystitis; Knowledge; Link; Membrane Proteins; Modification; Monoclonal Antibodies; NIH Program Announcements; Nature; Organ; Pain; Patients; Pelvic Pain; Pelvis; Personal Satisfaction; Play; Post-Translational Protein Processing; Printing; Process; Production; Proteins; Proteomics; Protocols documentation; Publishing; Recombinant Proteins; Reproducibility; Research; Research Personnel; Role; Sampling; Sensitivity and Specificity; Serum; Signal Transduction; Specificity; Specimen; Symptoms; Syndrome; Testing; Validation; Western Blotting; cell growth; cohort; density; human disease; interest; micturition urgency; migration; new technology; receptor; response; success; synthetic peptide; tool; urologic

DESCRIPTION (provided by applicant): 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. Interstitial Cystitis (IC) is a debilitating, chronic bladder syndrome characterized by urinary urgency, frequency, and pelvic/bladder pain. A current need in IC research is the identification of IC biomarkers, as there are presently no validated biomarkers for IC. The identification of IC biomarkers is important because they could potentially be used to create clinical tools for the diagnosis of IC and for the development of targeted treatments for IC patients. While the cause of IC is currently unknown, one possible contributor to this condition is worth noting: inflammation. Although autoimmunity is debated as a potential cause of IC, there is published evidence that suggests it may play a role in initiating or sustaining the chronic inflammatory response seen in this disease. Thus, the presence of inflammation/autoimmunity in IC may allow researchers to use the body's own immune response as a means of identifying biomarkers of IC. In this application, our goal is to identify biomarkers of IC by using antibodies from individual patients with IC.

描述（由申请人提供）：间质性膀胱炎（IC）是一种使人衰弱的慢性膀胱综合征。目前，还没有经过验证的IC生物标志物。然而，炎症与IC相关是公认的。虽然自身免疫作为一个潜在的原因是有争议的，IC的某些方面表明，它可能在启动或维持慢性炎症反应明显在这种疾病中发挥作用。例如，在IC患者血清中检测到的自身抗体的程度比对照组更高，IC中自身抗体识别的抗原种类表明发生的膀胱上皮细胞变性可能刺激自身抗体的产生。因此，IC中炎症/自身免疫的存在可以允许使用身体自身的免疫应答作为鉴定IC的生物标志物的手段。显然，这些潜在的自身抗原的知识可能会更好地使IC的病理生物学的更好的理解，并促进自身抗体的签名作为潜在的诊断生物标志物的开发或使用。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。来自自身免疫性疾病的经验表明，通常只有15-20%的患者表现出对任何给定抗原的应答。然而，蛋白质组学可能是成功的关键，因为它能够提供多重的手段。通过将对几种抗原的反应联系在一起，测试的灵敏度和特异性大大增加。最近，我们描述了一种“反向捕获”自身抗体微阵列的开发和使用，该微阵列是一种使用高密度单克隆抗体捕获阵列固定500种特异性抗原的平台。这些抗原靶标是参与信号转导、细胞周期调节、基因转录、凋亡、细胞生长、受体、膜蛋白以及粘附和迁移分子的蛋白质。使用固定化抗原作为“诱饵”，我们可以确定测试和对照之间的自身抗体对固定化抗原的反应性。我们相信这个平台可能非常适合IC的研究。因此，本申请的研究目的是：1）检验来自IC患者的血清自身抗体库可用于自身抗体谱分析的假设，和2）确定“反向捕获”自身抗体微阵列鉴定自身抗体标记作为IC生物标志物的可行性、稳健性和再现性。间质性膀胱炎（IC）是一种使人衰弱的慢性膀胱综合征，其特征为尿急、尿频和骨盆/膀胱疼痛。IC研究中的当前需要是IC生物标志物的鉴定，因为目前没有针对IC的经验证的生物标志物。IC生物标志物的鉴定是重要的，因为它们可能被用于创建用于IC诊断和IC患者靶向治疗的临床工具。虽然IC的原因目前尚不清楚，但这种情况的一个可能的贡献者值得注意：炎症。尽管自身免疫被认为是IC的潜在原因，但已发表的证据表明，它可能在引发或维持这种疾病中观察到的慢性炎症反应中发挥作用。因此，IC中炎症/自身免疫的存在可能允许研究人员使用身体自身的免疫反应作为鉴定IC生物标志物的手段。在本申请中，我们的目标是通过使用来自IC个体患者的抗体来鉴定IC的生物标志物。