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

基本信息

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
项目类别：
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

项目摘要

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.

狼疮性肾炎 (LN) 是一种免疫复合物介导的肾小球肾炎，影响多达三分之二的患者系统性红斑狼疮患者。尽管有标准的治疗方案，但病情进展大多数侵袭性形式的 LN（III 类和 IV 类）导致终末期肾衰竭的风险仍然很高。因此，有一个需要治疗反应的生物标志物，使医生能够更好地了解情况 LN 患者的治疗决策。为了解决这个问题，我们的提案建立在持续合作的基础上 MUSC 的临床肾病学小组与广泛的 LN 控制和治疗生物存储库之间的合作具有临床元数据的样本和 GlycoPath Inc.（一家开发独特的诊断公司）糖基化靶向液体活检测定。 GlycoPath 最近获得了专利、许可并发布了简化的抗体捕获载玻片阵列方法 GlycoTyper，可直接分析捕获的 N-聚糖血清和血浆糖蛋白，包括免疫球蛋白 G (IgG) 亚型。的改编 GlycoTyper 平台也已开发用于快速获取血清等生物液体的总聚糖谱和尿液。使用这种方法，几组患者的血清和尿液与对照和 LN 相匹配已对受试者的 N 连接聚糖成分进行了评估。一组独特的 LN 相关 N- 聚糖已被鉴定并作为拟议研究的基础。因为我们可以使用聚糖组来区分对照和 LN 条件，我们假设该测定可以用于监测接受标准护理疗法治疗的受试者的生物体液中的治疗反应如吗替麦考酚酯 (MMF)。在第一阶段 STTR 申请中，我们建议建立技术 Glycotyper-LNTx 用于监测 LN 治疗反应的优点和可行性。目标 1 将验证 N-聚糖 LN 受试者尿液样本中零时、3 个月和 12 个月时 MMF 治疗反应的概况的治疗。目标 2 将鉴定患者匹配的血清和尿液样本中的 IgG 特异性 N-聚糖谱在 LN 治疗反应队列中进行后续应用。本研究将建立并验证 LN 特定液体活检聚糖生物标志物测定用于监测疾病状态和治疗反应。