Hopkins Lupus Cohort

霍普金斯狼疮队列

• 批准号: 9080241
• 负责人: MICHELLE A PETRI
• 金额: $ 69.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-10 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9080241
• 关键词: Accounting; Affect; African American; Alpha Cell; American; Angiography; Atherosclerosis; Biological Markers; Biopsy; Calcified; Cardiovascular Diseases; Cardiovascular system; Caucasians; Chronic; Clinic; Clinic Visits; Clinical; Clinical Trials; Collaborations; Coronary; Coronary Arteriosclerosis; Coronary artery; Cyclophosphamide; Data; Detection; Disease; End stage renal failure; Event; Failure; Foundations; Future; Grant; Immune System Diseases; Individual; Interferon-alpha; Interferons; Investigation; Kidney; Kidney Diseases; Kidney Failure; Lead; Longitudinal Studies; Lupus; Lupus Nephritis; Measures; Medicine; Monitor; Mycophenolate; Nephritis; Organ; Outcome; Patients; Phase I Clinical Trials; Plasma Cells; Play; Procedures; Proteomics; Protocols documentation; Publishing; Randomized; Research Personnel; Resolution; Risk; Risk Factors; Role; Sampling; Sampling Studies; Serological; Site; Staging; Systemic Lupus Erythematosus; Testing; Time; Treatment outcome; United States National Institutes of Health; Urine; Validation; Vascular Cell Adhesion Molecule-1; Visit; Work; X-Ray Computed Tomography; belimumab; cardiovascular risk factor; clinical research site; cohort; experience; genetic signature; high risk; insight; interest; laboratory experiment; modifiable risk; mortality; neutrophil; patient subsets; predicting response; programs; public health relevance; trait; urinary

 DESCRIPTION (provided by applicant): The Hopkins Lupus Cohort is a unique 27 year, 2300 SLE patient longitudinal cohort in which patients are followed by protocol every 3 months, allowing study of time-varying (lupus activity, cardiovascular risk factors and, treatment) variables: 1) In the last RO-1 we successfully developed and published computed tomography angiography (CTA) for detection of noncalcified plaque in SLE and showed that it was associated with same day measures of SLE activity. In this project, we will determine predictors of noncalcified plaque changes over time. We will bring an automated measure of noncalcified and calcified plaque burden to the clinic. 2) In the last RO-1 we successfully developed a consortium of U.S. sites interested in urine biomarkers of lupus nephritis activity, and discovered and published new biomarkers including urinary VCAM-1. In this project we have enlarged the consortium, arranged collaboration with the GlaxoSmithKline belimumab lupus nephritis clinical trial to obtain longitudinal samples, and have begun our own urinary proteomics discovery program. We have already successfully brought urinary TWEAK to clinical trial stage, and anticipate bringing a panel of urinary biomarkers to the clinic for identification of lupus nephrits activity and prediction of treatment outcome. 3) In a past collaboration with Biogen-Idec we found that BAFF and neutrophil gene signatures associate with same day SLE activity and predict activity over the next year. In this project, we will continue that collaboration and determine whether these gene signatures are invariant in an individual or whether they change over time. If they change, we will evaluate the contributions of treatments and other variables. These investigations will demonstrate the utility of these signatures in indicating and predicting disease activity over time, so that they can be used in the clinic and in clinical trials.

 描述（由申请人提供）：霍普金斯狼疮队列是一个独特的27年、2300例SLE患者纵向队列，其中患者每3个月接受一次方案随访，允许研究随时间变化的（狼疮活动、心血管危险因素和治疗）变量：1）在上一次RO-1中，我们成功开发并发表了计算机断层扫描血管造影（CTA）用于检测SLE患者的非钙化斑块，并显示其与当天测量的SLE活动相关。在这个项目中，我们将确定非钙化斑块随时间变化的预测因子。我们将为临床带来非钙化和钙化斑块负荷的自动测量。2)在上一个RO-1中，我们成功地开发了一个对狼疮肾炎活动的尿液生物标志物感兴趣的美国网站联盟，并发现 并发表了包括尿VCAM-1在内的新生物标志物。在这个项目中，我们扩大了联盟，安排与葛兰素史克贝利木单抗狼疮肾炎临床试验合作，以获得纵向样本，并开始了我们自己的尿蛋白质组学发现计划。我们已经成功地将尿TWEAK带入临床试验阶段，并预计将一组尿生物标志物带入临床，用于识别狼疮肾炎活动和预测治疗结果。3)在过去与Biogen-Idec的合作中，我们发现BAFF和中性粒细胞基因特征与当天的SLE活动相关，并预测下一年的活动。在这个项目中，我们将继续合作，并确定这些基因签名在个体中是否不变，或者它们是否会随着时间的推移而变化。如果它们发生变化，我们将评估治疗和其他变量的贡献。这些研究将证明这些特征在指示和预测疾病活动性方面的效用，以便它们可以用于临床和临床试验。