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.

摘要 伊加肾病（IgAN）是最常见的原发性肾小球肾炎，是肾脏损害的重要原因， 失败它是一种系膜增生性肾小球疾病，由特征性IgA 1系膜沉积物定义。 这些系膜沉积物可能来源于含有半乳糖的IgA 1的循环免疫复合物 由IgG自身抗体结合的（Gal）缺陷型O-聚糖（Gd-IgA 1）。发病机制模型描述 IgAN作为一种自身免疫性疾病是基于发现与Gd-IgA 1结合的IgG自身抗体。 在伯明翰的亚拉巴马大学（UAB）的Jan Novak博士的实验室。作为这些研究的一部分，博士。 Novak的实验室开发了用于检测和定量评估Gd-IgA 1和IgG的检测方法 自身抗体使用这些测定法分析来自几个IgAN患者队列的血清样品， 已发表; Gd-IgA 1测定和IgG自身抗体测定都有可能作为 IgAN的临床前检测、结果预测和对治疗反应的监测。既定 IgAN的发病机制模型使制药业能够开始开发和测试治疗IgAN的方法。 疾病然而，只有次要标记（例如，蛋白尿和估计肾小球滤过率[eGFR]） 目前被用作终点，增加了临床试验的时间和成本。因此，临床级测试， 评估主要致病标志物是迫切需要的。为了满足这一要求，我们已授权 UAB的知识产权，围绕诺瓦克博士实验室开发的IgAN测定。目标 该提案的目的是表征和验证IgG自身抗体检测试剂盒的组分，并建立 标准操作规程（SOP），以便可以验证和商业化用于临床。