Kidney involvement in human SLE is common and usually severe. Although current immunosuppressive drugs can control renal SLE, therapy would be more effective with less toxicity if the onset, severity, or responsiveness of lupus renal flares could be predicted, and treatment modified accordingly. Presently there are no clinically validated biomarkers that can be used to reliably monitor SLE renal activity throughout the flare cycle. However, recent data from this laboratory show that levels of the chemokine monocyte chemoattractant protein-1 (MCP-1) increase significantly in the urine of patients having a renal flare, and appear to reflect disease activity and severity. It was thus postulated that urine MCP-1 (uMCP-1) is a lupus nephritis biomarker that reflects the level of kidney inflammation, and that can be used to predict impending flare, flare severity, and flare prognosis. The purpose of this investigation is to validate uMCP-1 as a biomarker of SLE nephritis flare cycles and renal inflammation. The study goals will be addressed through two Specific Aims that utilize the Ohio SLE Study (OSS) database and specimen bank, developed at Ohio State University. The OSS contains clinical information and serial urine samples from a cohort of well-characterized SLE patients followed prospectively every 2 months over several years.
In Aim 1, uMCP-1 levels will be measured by ELISA in samples obtained before, during, and after SLE renal flares, and correlated to clinical course. The sensitivity and specificity of uMCP-1 as a predictor of flare onset, severity, and response to therapy will be calculated, and the interaction of uMCP-1 with traditional clinical markers of SLE will be assessed.
In Aim 2, uMCP-1 measured at kidney biopsy will be correlated with infiltrating renal leukocytes, glomerular crescents, glomerulosclerosis, interstitial fibrosis, and tubular atrophy, to determine whether uMCP-1 levels reflect specific renal lesions found in SLE nephritis that can affect kidney survival. To test whether uMCP-1 correlates better with renal inflammation or fibrosis, the strength of the association of uMCP-1 and renal inflammation will be compared to the strength of the association of uMCP-1 and renal fibrosis. In summary, this project is expected to demonstrate that uMCP-1 is a valid biomarker of lupus nephritis and its flare, and can be used to facilitate treatment decisions.
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