We have assembled 1,000 SLE subjects in a registry, and they are now being entered into a research repository. Our initial efforts are focused on preclinical disease in first-degree relatives (a genetically enriched cohort likely to evolve into Systemic Lupus Erythematosus) in order to examine which biomarkers and genes will predict the onset of clinical Systemic Lupus Erythematosus (SLE). In collaboration with the Cedars-Sinai Department of Pathology and Laboratory Medicine, we are examining candidate genes in stored clinical specimens (kidney biopsy tissue) that we can associate with the most severe clinical SLE phenotype.
It is well recognized that premature ischemic heart disease is a cause of increased SLE mortality and occurs with great frequency, along with angina chest pain, in SLE subjects. Our preliminary studies revealed that microvascular ischemic heart disease is prevalent in SLE women who have chest pain and do not have evidence of macrovascular (large vessel) coronary artery disease. This discovery could be a potential link between a vexing clinical problem (premature ischemic heart disease in SLE women) and a potential mechanism that might be amenable to treatment. Finally, we have observed a significant degree of clinical depression, accounting for a major impact on the quality of life in the underserved, largely Hispanic SLE patients in Southern California, through our collaborations with Community Health Services in the UCLA Fielding School of Public Health, Harbor - UCLA Medical Center, University of Southern California and Loma Linda University. These data have contributed to at least four multidisciplinary and multi-institutional reports that have been published in major journals that speak to clinicians, health service researchers and bio-psychologists.
Achievements in SLE
Heart disease in the SLE population has drawn our considerable attention, and we have embarked on a series of studies to understand its relationship to inflammation and other SLE- related factors using a sensitive detection method (cardiac magnetic resonance imaging, or CMRI) to evaluate microvascular coronary dysfunction. We enrolled 20 SLE women with angina and no prior documented coronary artery disease (CAD) and 10 reference control women in a pilot study to evaluate the presence of myocardial ischemia measured by adenosine-stress CMRI perfusion abnormalities. All patients underwent coronary computed tomography angiography (CCTA). Among patients with complete data, 44 percent displayed evidence of CMRI reversible perfusion abnormality but no evidence of obstructive CAD on CCTA. Framingham risk scores were low, and traditional risk factors did not predict these findings; multivariable linear regression identified SLE as the only significant predictor of the results. We propose that these findings are extremely relevant and can be used to justify further studies including the possibility of disease prevention.
Program Interactions in SLE
- Cedars-Sinai Heart Institute — Noel Bairey Merz, MD, FACC; Puja Mehta, MD, FACC; Chrisandra Shufelt, MD, MS, NCMP; Yuching Yang, PhD; Tim Henry, MD; PK Shah, MD; Jay Schapira, MD
- Cedars-Sinai S. Mark Taper Foundation Imaging Center — Daniel Berman, MD; Louise Thomson, MBChB; Barry Pressman, MD
- Oklahoma Medical Research Foundation — Judith James, MD; Eliza Chakravarty, MD; Swapan Nath, PhD
- St. Luke's Medical Center, Manila, Philippines — Sandra Navarra, MD; Evan Vista, MD
- Loma Linda Medical Center — Emmanuel Katsaros, DO; Ioana Moldovan, MD
- UCLA — Perry Nicassio, PhD
- Harbor - UCLA Medical Center — George Karpouzas, MD; Dilrukshie Cooray, MD; Sharon Adler, MD
- University of Southern California — Karina Torralba, MD; Shuntaro Shinada, MD; William Stohl, MD