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.

Public Health Relevance

The Hopkins Lupus Cohort is a longitudinal study of over 2,300 SLE patients followed every 3 months by protocol. This project explores three new outcomes: 1) predicting how a measure of coronary artery atherosclerosis, noncalcified plaque, changes over time; 2) tracking renal activity through urine biomarkers and 3) determining how gene signatures contribute to disease activity and organ damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR069572-01
Application #
9080241
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Witter, James
Project Start
2016-09-10
Project End
2021-07-31
Budget Start
2016-09-10
Budget End
2017-07-31
Support Year
1
Fiscal Year
2016
Total Cost
$1,489,420
Indirect Cost
$534,479
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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Duarte-García, Alí; Barr, Erik; Magder, Laurence S et al. (2017) Predictors of incident proteinuria among patients with SLE. Lupus Sci Med 4:e000200
Wolf, Bethany J; Spainhour, John C; Arthur, John M et al. (2016) Development of Biomarker Models to Predict Outcomes in Lupus Nephritis. Arthritis Rheumatol 68:1955-63