Modeling SLE Nephritis Through Urine MCP-1

通过尿液 MCP-1 模拟 SLE 肾炎

• 批准号: 7367549
• 负责人: BRAD H ROVIN
• 金额: $ 20.25万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-08 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7367549
• 关键词: Address; Affect; Atrophic; Biological Markers; Biopsy; CCL2 gene; Clinical; Clinical Markers; Complication; Control Groups; Data; Databases; Disease; Enzyme-Linked Immunosorbent Assay; Fibrosis; Flare; Goals; Human; Immunosuppressive Agents; Individual; Inflammation; Injury; Invasive; Investigation; Kidney; Kidney Diseases; Laboratories; Lesion; Leukocytes; Lupus; Lupus Nephritis; Measurement; Measures; Mediating; Mediator of activation protein; Modeling; Monitor; Monocyte Chemoattractant Protein-1; Morbidity - disease rate; Nephritis; Nephrosclerosis; Numbers; Ohio; Pathogenesis; Pathology; Patients; Pharmaceutical Preparations; Phase; Phenotype; Purpose; Resources; Sampling; Sensitivity and Specificity; Serum; Severities; Specimen; Systemic Lupus Erythematosus; Systemic Therapy; Testing; Therapeutic; Therapeutic immunosuppression; Toxic effect; Tubular formation; Universities; Urine; Validation; chemokine; cohort; glomerulosclerosis; interstitial; outcome forecast; prospective; response

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：人类SLE的肾脏受累很常见，通常很严重。虽然目前的免疫抑制药物可以控制肾脏系统性红斑狼疮，治疗将是更有效的毒性更小，如果发病，严重程度，或狼疮肾耀斑的反应可以预测，并相应地修改治疗。目前还没有临床验证的生物标志物可用于可靠地监测整个发作周期的SLE肾活动。然而，来自该实验室的最新数据显示，趋化因子单核细胞趋化蛋白-1（MCP-1）的水平在具有肾耀斑的患者的尿液中显著增加，并且似乎反映疾病的活动性和严重程度。因此，假设尿MCP-1（uMCP-1）是反映肾脏炎症水平的狼疮肾炎生物标志物，并且可用于预测即将发生的发作、发作严重性和发作预后。本研究的目的是验证uMCP-1作为SLE肾炎发作周期和肾脏炎症的生物标志物。研究目标将通过两个特定目标来实现，这两个特定目标利用了俄亥俄州SLE研究（OSS）数据库和标本库，由俄亥俄州州立大学开发。OSS包含临床信息和连续尿样，这些尿样来自一组特征明确的SLE患者，这些患者在几年内每2个月前瞻性随访一次。在目标1中，将通过ELISA测量在SLE肾发作之前、期间和之后获得的样品中的uMCP-1水平，并将其与临床过程相关联。将计算uMCP-1作为发作、严重程度和对治疗的反应的预测因子的灵敏度和特异性，并将评估uMCP-1与SLE的传统临床标志物的相互作用。在目标2中，在肾活检中测量的uMCP-1将与浸润性肾白细胞、肾小球新月体、肾小球硬化、间质纤维化和肾小管萎缩相关，以确定uMCP-1水平是否反映在SLE肾炎中发现的可影响肾存活的特异性肾病变。为了测试uMCP-1是否与肾脏炎症或纤维化更好地相关，将uMCP-1与肾脏炎症的关联强度与uMCP-1与肾脏纤维化的关联强度进行比较。总之，该项目有望证明uMCP-1是狼疮肾炎及其发作的有效生物标志物，并可用于促进治疗决策。