Hopkins Lupus Cohort

 描述(申请人提供)：霍普金斯狼疮队列是一个独一无二的27年、2300名SLE患者纵向队列，每3个月对患者进行一次方案跟踪，允许研究时变(狼疮活动、心血管风险因素和治疗)变量：1)在最近的RO-1中，我们成功地开发并发表了用于检测SLE非钙化斑块的计算机断层扫描血管成像(CTA)，并表明它与SLE活动的当天测量有关。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。我们将把非钙化和钙化斑块负荷的自动化测量带到临床。2)在上一个RO-1中，我们成功地开发了一个对狼疮性肾炎活动的尿液生物标记物感兴趣的美国站点联盟，并发现 并公布了包括尿VCAM-1在内的新生物标志物。在这个项目中，我们扩大了联合体，安排与葛兰素史克的Belimumab狼疮性肾炎临床试验合作，获得纵向样本，并开始了我们自己的尿蛋白组学发现计划。我们已经成功地将尿液Twike带入临床试验阶段，并期待将一组尿液生物标志物带到临床上，以识别狼疮肾的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和中性粒细胞基因签名与当天的SLE活动有关，并预测明年的活动。在这个项目中，我们将继续这种合作，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。这些研究将展示这些标记在指示和预测疾病随时间推移的活动方面的实用性，以便它们可以在临床和临床试验中使用。

 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.