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:
- 金额:$ 27.54万
- 依托单位:
- 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:
- 关键词:AddressAffectAminesAnti-Inflammatory AgentsAntibodiesAntigen-Antibody ComplexAsparagineAutoimmune DiseasesBiological AssayBiological MarkersCellsChronicClinicClinicalCollaborationsDataDiagnosticDiseaseEnd stage renal failureGlomerulonephritisGlycoproteinsIgG1IgG2IgG3IgG4Immune Complex DiseasesImmunoglobulin GImmunoglobulinsImmunosuppressionIn complete remissionInflammatory ResponseJointsKidney TransplantationLegal patentLicensingLinkLung TransplantationLupus NephritisMediatingMetadataMethodsModificationMonitorNephrologyOrganOutcomeParentsPatientsPeptide N-glycohydrolase FPeripheralPhasePhysiciansPlasmaPolysaccharidesPrediction of Response to TherapyPropertyPublishingReportingSamplingSerumSlideSmall Business Technology Transfer ResearchSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationSpottingsSystemic Lupus ErythematosusTestingTherapeuticTimeTissuesTreatment ProtocolsUrinebiobankbiomarker panelclinical translationcohortfollow-upglycosylationimmunoregulationliquid biopsymycophenolate mofetilpatient subsetspredicting responseprofiles in patientsresponsestandard carestandard of caresugartreatment 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,
系统性红斑狼疮患者。尽管有标准的治疗方案,
最具侵袭性的LN(III和IV类)至终末期肾衰竭的发病率仍然很高。由此可见,有一
需要治疗反应的生物标志物,使医生能够更好地了解
LN患者的治疗决策。为了解决这个问题,我们的建议建立在正在进行的合作基础上。
MUSC的临床肾病组与广泛的LN生物储存库之间的对照和治疗
样本与临床元数据和GlycoPath Inc.,一家诊断公司,
糖基化靶向液体活检测定。GlycoPath最近获得了专利,许可并发布了一个
简化的抗体捕获载玻片阵列方法,GlycoTyper,用于直接分析捕获的
血清和血浆糖蛋白,包括免疫球蛋白G(IgG)亚型。改编自
GlycoTyper平台也已开发用于快速获得血清等生物流体的总聚糖谱
和尿液。使用这种方法,几组患者的血清和尿液与对照组和LN患者的血清和尿液相匹配。
已对受试者的N-连接聚糖成分进行了评价。一组不同的LN相关N-
已经鉴定了聚糖,并将其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
用于监测接受标准治疗的受试者的生物液体中的治疗反应
比如吗替麦考酚酯(MMF)。在第一阶段的短期信托登记申请中,我们建议设立
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
0、3个月和12个月时LN受试者尿液样本的MMF治疗应答曲线
的治疗。目标2将鉴定患者匹配血清和尿液样本中的IgG特异性N-聚糖谱
并在LN治疗反应队列中随访应用。本研究将建立并验证LN特定
用于监测疾病状态和治疗反应的液体活检聚糖生物标志物测定。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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专利数量(0)
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Stephen Castellino的其他文献
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{{ truncateString('Stephen Castellino', 18)}}的其他基金
Development of the GlycoHCCTyper for the early detection of HCC
开发用于早期检测 HCC 的 GlycoHCCTyper
- 批准号:
10382624 - 财政年份:2022
- 资助金额:
$ 27.54万 - 项目类别:
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