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 #
5R01AR043727-14
Application #
8460769
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Witter, James
Project Start
1996-09-30
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
14
Fiscal Year
2013
Total Cost
$608,985
Indirect Cost
$203,720
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Baer, Alan N; Petri, Michelle; Sohn, Jungsan et al. (2016) Antibodies to interferon-inducible protein-16 in primary Sjögren's syndrome are associated with markers of more severe diseas. Arthritis Care Res (Hoboken) :
Kiani, A N; Aukrust, P; Ueland, T et al. (2016) Serum osteoprotegrin (OPG) in subclinical atherosclerosis in systemic lupus erythematosus. Lupus :
Wang, Yuchuan; Coughlin, Jennifer M; Ma, Shuangchao et al. (2016) Neuroimaging of translocator protein in patients with systemic lupus erythematosus: a pilot study using [11C]DPA-713 positron emission tomography. Lupus :
Lloyd, Thomas E; Christopher-Stine, Lisa; Pinal-Fernandez, Iago et al. (2016) Cytosolic 5'-Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases. Arthritis Care Res (Hoboken) 68:66-71
Baer, Alan N; Petri, Michelle; Sohn, Jungsan et al. (2016) Association of Antibodies to Interferon-Inducible Protein-16 With Markers of More Severe Disease in Primary Sjögren's Syndrome. Arthritis Care Res (Hoboken) 68:254-60
Hanly, John G; O'Keeffe, Aidan G; Su, Li et al. (2016) The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology (Oxford) 55:252-62
Domingues, Vinicius; Magder, Laurence S; Petri, Michelle (2016) Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE. Lupus Sci Med 3:e000107
Zollars, Eric; Courtney, Sean M; Wolf, Bethany J et al. (2016) Clinical Application of a Modular Genomics Technique in Systemic Lupus Erythematosus: Progress towards Precision Medicine. Int J Genomics 2016:7862962
Kim, Mimi Y; Buyon, Jill P; Guerra, Marta M et al. (2016) Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study. Am J Obstet Gynecol 214:108.e1-108.e14
Durcan, L; Petri, M (2016) Immunomodulators in SLE: Clinical evidence and immunologic actions. J Autoimmun 74:73-84

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