Glycan biomarker panels in liquid biopsies for predicting treatment response in lupus nephritis

液体活检中的聚糖生物标志物组用于预测狼疮性肾炎的治疗反应

• 批准号: 10601270
• 负责人: Stephen Castellino
• 金额: $ 27.54万
• 依托单位: GLYCOPATH, INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10601270
• 关键词: Address; Affect; Amines; Anti-Inflammatory Agents; Antibodies; Antigen-Antibody Complex; Asparagine; Autoimmune Diseases; Biological Assay; Biological Markers; Cells; Chronic; Clinic; Clinical; Collaborations; Data; Diagnostic; Disease; End stage renal failure; Glomerulonephritis; Glycoproteins; IgG1; IgG2; IgG3; IgG4; Immune Complex Diseases; Immunoglobulin G; Immunoglobulins; Immunosuppression; In complete remission; Inflammatory Response; Joints; Kidney Transplantation; Legal patent; Licensing; Link; Lung Transplantation; Lupus Nephritis; Mediating; Metadata; Methods; Modification; Monitor; Nephrology; Organ; Outcome; Parents; Patients; Peptide N-glycohydrolase F; Peripheral; Phase; Physicians; Plasma; Polysaccharides; Prediction of Response to Therapy; Property; Publishing; Reporting; Sampling; Serum; Slide; Small Business Technology Transfer Research; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spottings; Systemic Lupus Erythematosus; Testing; Therapeutic; Time; Tissues; Treatment Protocols; Urine; biobank; biomarker panel; clinical translation; cohort; follow-up; glycosylation; immunoregulation; liquid biopsy; mycophenolate mofetil; patient subsets; predicting response; profiles in patients; response; standard care; standard of care; sugar; treatment response

Lupus nephritis (LN), an immune complex-mediated glomerulonephritis, affects up to two-thirds of patients with systemic lupus erythematosus. Despite standard treatment protocols, progression of the most aggressive forms of LN (class III and IV) to end-stage renal failure remains high. Thus, there is a need for biomarkers of therapeutic response that would allow physicians to make better-informed treatment decisions for LN patients. To address this, our proposal builds upon ongoing collaborations between a clinical nephrology group at MUSC with an extensive LN biorepository of control and treatment samples with clinical metadata and GlycoPath Inc., a diagnostic company developing unique glycosylation targeted liquid biopsy assays. GlycoPath has recently patented, licensed and published a streamlined antibody capture slide array approach, GlycoTyper, to directly profile N-glycans of captured serum and plasma glycoproteins including imm unoglobulin G (IgG) subtypes. An adaption of the GlycoTyper platform has also been developed to rapidly obtain total glycan profiles of biofluids like serum and urine. Using this approach, several cohorts of patient matched serum and urine from control and LN subjects have been evaluated for N-linked glycan constituents. A distinct panel of LN associated N- glycans have already been identified and serve as the basis for the proposed studies. Because we can use glycan panels to distinguish control from LN conditions, we hypothesize that this assay can be applied to monitor treatment response in biofluids from subjects treated with standard-of-care therapies like mycophenolate mofetil (MMF). In this Phase I STTR application, we propose to establish the technical merit and feasibility of Glycotyper-LNTx for monitoring LN treatment responses. Aim 1 will validate N-glycan profiles in urine samples from LN subjects for MMF treatment response at time zero, 3 months and 12 months of treatment. Aim 2 will identify IgG specific N-glycan profiles in patient matched serum and urine samples with follow up application in a LN treatment response cohort. This study will establish and validate a LN specific liquid biopsy glycan biomarker assay for use in monitoring disease status and therapeutic response.

狼疮肾炎（LN）是一种免疫复合介导的肾小球肾炎，影响多达三分之二的 全身性红斑狼疮的患者。尽管标准治疗方案，但 最激进的LN（III和IV级）到末期肾衰竭仍然很高。因此，有一个 需要治疗反应的生物标志物，这将使医生能够做出更有信息 LN患者的治疗决定。为了解决这个问题，我们的建议基于正在进行的合作 在MUSC的临床肾脏科组之间具有广泛的LN生物疗法和治疗 临床元数据和Glycopath Inc.的样品，诊断公司开发独特的公司 糖基化靶向液体活检测定法。糖剂最近已获得专利，许可和出版 简化的抗体捕获幻灯片阵列方法Glycotyper直接介绍了捕获的n-glycans 血清和血浆糖蛋白，包括IMM非果蛋白G（IgG）亚型。改编 还开发了糖基质平台，以快速获得血清（如血清）的总聚糖概况 和尿液。使用这种方法，来自对照和LN的几个患者匹配的血清和尿液匹配 已经评估了受试者的N连接聚糖成分。 LN相关的n-独特面板 聚糖已经被鉴定出来并作为拟议研究的基础。因为我们可以 使用聚糖面板将控制与LN条件区分开，我们假设该测定可能是 用于监测接受标准疗法治疗的受试者的生物流体中的治疗反应 像霉酚酸酯（MMF）一样。在此阶段I STTR应用程序中，我们建议建立技术 糖基质 - LNTX在监测LN治疗反应中的优点和可行性。 AIM 1将验证n-Glycan LN受试者的尿液样品中的MMF治疗反应的尿液样本，3个月和12个月 治疗。 AIM 2将在患者匹配的血清和尿液样本中识别IgG特定的N-聚糖特征 在LN治疗反应队列中随访。这项研究将建立并验证特定于LN 液体活检聚糖生物标志物分析用于监测疾病状态和治疗反应。