Foreboding Lupus Nephritis in Minority Woman

描述(申请人提供)：狼疮是一种系统性自身免疫性疾病，在遗传学和免疫学起源上是复杂的。肾脏疾病是狼疮发病率和死亡率的主要原因，特别是在少数族裔妇女中。虽然连续肾活检在密切监测狼疮性肾炎的进展方面可能是理想的，但它可能不实用或不可行。因此，这些研究的长期目标是确定可能对监测狼疮肾脏疾病进展有用的潜在生物标志物。使用不同的蛋白质组学方法，我们已经发现了抗体介导的肾炎期间出现在尿液中的几个分子。我们完成的横断面研究已经帮助在小鼠和狼疮患者的尿液中发现了6个潜在的生物标记物候选。在这项建议中，我们将对狼疮患者队列进行纵向研究，其中90%是少数族裔个体，以确定与目前使用的实验室标准相比，是否有任何尿液生物标记物候选可能在预测红斑狼疮、严重组织性肾炎或终末期肾病方面更好。此外，我们建议建立这些生物标志物对狼疮性肾炎以及其他导致蛋白尿和肾炎的原因的特异性。鉴于狼疮终末期肾病的高发病率，早期诊断和及时治疗是绝对必要的。在这些患者的尿液中发现更具预测性的生物标志物可能会对狼疮性肾炎的临床治疗产生深远的影响。公共卫生相关性：鉴于少数民族狼疮妇女终末期肾脏疾病的高发病率，早期诊断和及时治疗是绝对必要的。这些患者尿液中替代生物标志物的鉴定将对狼疮性肾炎的临床治疗产生深远的影响。最后，确定其中一些生物标志物的致病作用，可能为更好地治疗这种疾病铺平道路。

DESCRIPTION (provided by applicant): Lupus is a systemic autoimmune disease that is complex in genetics and its immunological origins. Renal disease is a leading cause of morbidity and mortality in lupus, particularly among minority women. Although serial renal biopsies may be ideal in closely monitoring the progression of lupus nephritis, it may not be practical or feasible. Hence, the long-term goal of these studies is to identify potential biomarkers that may be of use in monitoring the progression of renal disease in lupus. Using different proteomic approaches, we have uncovered several molecules that appear in the urine during antibody-mediated nephritis. Our completed cross-sectional studies have helped uncover 6 potential biomarker candidates in the urine of mice and patients with lupus. In this proposal, we will study a cohort of lupus patients, 90% of whom are minority individuals, in a longitudinal fashion in order to determine if any of the urinary biomarker candidates might be better at predicting flares, severe histological nephritis, or end stage renal disease, compared to currently used laboratory yardsticks. In addition, we propose to establish the specificity of these biomarkers for lupus nephritis, as well as other causes of proteinuria and nephritis. Given the high incidence of end stage renal disease in lupus, early diagnosis and prompt treatment is absolutely essential. Identification of more predictive biomarkers in the urine of these patients could have a profound impact on the clinical management of lupus nephritis. PUBLIC HEALTH RELEVANCE: Given the high incidence of end stage renal disease in minority women with lupus, early diagnosis and prompt treatment is absolutely essential. Identification of surrogate biomarkers in the urine of these patients could have a profound impact on the clinical management of lupus nephritis. Finally, establishing the pathogenic roles of some of these biomarkers, may pave the way towards better therapy for this disease.