Traditional cardiovascular risk factors do not entirely account for the increased risk of atherosclerosis, the major cause of death, in systemic lupus erythematosus (SLE). In this project we want to identify new pathogenic pathways of atherosclerosis in SLE patients, by assessing the association between newly identified potential risk factors and a refined measure of subclinical atherosclerosis, soft (noncalcified) coronary plaque. Similarly over 50% of SLE patients develop lupus nephritis, including 75% of African-American SLE patients. Renal biopsy is the gold standard to determine renal activity, but is expensive, invasive, and has real risk to the patient. We hypothesize that urinary markers of renal activity will have clinical utility in human lupus nephritis, as they have in renal transplant patients and murine models of SLE. In addition we want to develop and study three new approaches to assess hypercoagulability risk (endogenous thrombogenic potential, complement activation, and platelet microparticles) to determine if these markers can predict future thrombotic events or associated with antiphospholipid antibodies.

Public Health Relevance

Although the survival of SLE patients has greatly improved, permanent organ damage continues to occur in the general public. This project addresses three challenges: hardening of the arteries, blood clots, and lupus kidney disease in collaboration with other rheumatologists and radiologists.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR043727-13
Application #
8128441
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Witter, James
Project Start
1996-09-30
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
13
Fiscal Year
2012
Total Cost
$641,036
Indirect Cost
$214,442
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Akhter, Ehtisham; Shums, Zakera; Norman, Gary L et al. (2013) Utility of antiphosphatidylserine/prothrombin and IgA antiphospholipid assays in systemic lupus erythematosus. J Rheumatol 40:282-6
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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