The Hopkins Lupus Cohort is a unique 25 year, 2000 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 non-calcified plaque in SLE and showed that it was associated with same day measures of SLE activity. In this RO-1, we will determine predictors of non-calcified plaque changes over time. We will bring an automated measure of non-calcified 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 RO-1 we have enlarged the consortium, arranged collaboration with the Glaxo Smith Kline 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 RO-1, 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.
The Hopkins Lupus Cohort is a longitudinal study of over 2,000 SLE patients followed every 3 months by protocol. This RO-1 explores three new outcomes: 1) predicting how a measure of coronary artery atherosclerosis, non-calcified plaque, changes over time;2) tracking renal activity through urine biomarkers and 3) determining how gene signatures contribute to disease activity and organ damage.
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|Sakurai, Daisuke; Zhao, Jian; Deng, Yun et al. (2013) Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression. PLoS Genet 9:e1003870|
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