Utilizing IgG Autoantibodies as Biomarkers in IgA Nephropathy

利用 IgG 自身抗体作为 IgA 肾病的生物标志物

• 批准号: 10081000
• 负责人: William J. Placzek
• 金额: $ 21.17万
• 依托单位: RELIANT GLYCOSCIENCES LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10081000
• 关键词: Address; Alabama; Antigen-Antibody Complex; Asians; Autoantibodies; Autoimmune Diseases; Automobile Driving; Binding; Biological Assay; Biological Markers; Caucasians; Characteristics; Chronic Kidney Failure; Clinical; Clinical Trials; Complex; Deposition; Detection; Development; Diagnosis; Disease; Drug Industry; Galactose; Glomerular Filtration Rate; Glomerulonephritis; Goals; IGA Glomerulonephritis; IgA1; Immune; Immunoglobulin G; Injury to Kidney; Intellectual Property; Kidney; Kidney Failure; Laboratories; Measurement; Mediating; Modeling; Molecular; Monitor; Pathogenesis; Pathogenicity; Patients; Phase; Polysaccharides; Population; Procedures; Production; Proteinuria; Publishing; Reagent; Renal glomerular disease; Reproducibility; Research; Research Personnel; Sampling; Serum; Testing; Time; Universities; Validation; base; cohort; commercialization; cost; improved; outcome prediction; pre-clinical; response; specific biomarkers

Abstract IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of kidney failure. It is a mesangioproliferative glomerular disease defined by characteristic IgA1 mesangial deposits. These mesangial deposits likely originate from circulating immune complexes that contain IgA1 with Galactose (Gal)-deficient O-glycans (Gd-IgA1) that are bound by IgG autoantibodies. The pathogenesis model describing IgAN as an autoimmune disease was based on the discovery of IgG autoantibodies that bind Gd-IgA1 in the laboratory of Dr. Jan Novak at the University of Alabama at Birmingham (UAB). As part of these studies, Dr. Novak's laboratory developed assays for the detection and quantitative assessment of both Gd-IgA1 and IgG autoantibodies. The use of these assays for analysis of serum samples from several cohorts of IgAN patients has been published; both the Gd-IgA1 assay and the IgG autoantibody assay have potential as markers for preclinical detection of IgAN, prediction of outcome, and monitoring the response to therapy. The established pathogenesis model of IgAN enabled pharmaceutical industry to start developing and testing treatment for the disease. However, only secondary markers (e.g., proteinuria and estimated glomerular filtration rate [eGFR]) are currently used as the endpoints, adding to the time and cost of clinical trials. Thus, clinical-grade tests that assess primary causative markers are urgently needed. To address this requisite, we have licensed the intellectual property from UAB that surrounds the IgAN assays developed in Dr. Novak's laboratory. The goal of this proposal is to characterize and validate the components of the IgG autoantibody assay and establish standard operating procedures (SOPs) so that it can be validated and commercialized for clinical use.

抽象的 IGA肾病（IGAN）是最常见的原发性肾小球肾炎，也是肾脏的重要原因 失败。它是一种由特征性IgA1肾小球沉积物定义的肾小球增生性肾小球疾病。 这些肾小球沉积物可能起源于循环中的免疫复合物，这些免疫复合物含有带有半乳糖的IgA1 （GAL） - 缺乏IgG自身抗体约束的缺陷O-Glycans（GD-IGA1）。描述的发病机理模型 Igan作为一种自身免疫性疾病是基于发现与GD-IGA1结合的IgG自身抗体的发现 伯明翰（UAB）的阿拉巴马大学Jan Novak博士实验室。作为这些研究的一部分，博士 诺瓦克的实验室开发了用于检测和定量评估GD-IGA1和IgG的测定法 自动抗体。这些测定法用于分析来自几个IGAN患者的血清样品 已出版； GD-IGA1分析和IgG自身抗体测定都有可能作为标记 临床前检测Igan，预测结果以及监测对治疗的反应。已建立 Igan的发病机理模型使制药行业能够开始开发和测试治疗 疾病。但是，仅次级标记（例如蛋白尿和估计的肾小球过滤率[EGFR]） 目前用作终点，增加了临床试验的时间和成本。因此，临床级测试 迫切需要评估主要的致病标记。为了解决这一必要条件，我们已许可 诺瓦克博士实验室中开发的IGAN分析的UAB的知识产权。目标 该提案的表征和验证IgG自身抗体测定的组件并建立 标准操作程序（SOP），以便可以对其进行验证和商业化以供临床使用。