a Divisions of Rheumatology, Department of Pediatrics , University of Cincinnati College of Medicine , Cincinnati , OH , USA.
b Division of Nephrology & Hypertension, Department of Pediatrics , University of Cincinnati College of Medicine , Cincinnati , OH , USA.
Expert Rev Proteomics. 2019 Apr;16(4):303-313. doi: 10.1080/14789450.2019.1592681. Epub 2019 Mar 18.
Lupus nephritis (LN) is a common and significant manifestation, affecting 60% of adults and 80% of children with systemic lupus erythematosus, with up to 30% of patients progressing to end stage renal disease. There remains an unmet need for non-invasive markers of disease activity, damage, and response to therapy. In addition, non-invasive biomarkers that predict therapeutic efficacy are needed to enable cost-effective clinical trials of novel agents. Areas covered: This review examines the methodological aspects of urinary proteomics, the role of proteome profiling in identifying promising urinary biomarkers in LN, and the translation of research findings into clinically useful tools in the management of LN. Expert opinion: Targeted and unbiased proteomics have identified several promising urinary biomarkers that predict LN activity, damage (chronicity), and response to therapy. In particular, a combination of biologically plausible urinary biomarkers termed as RAIL (Renal Activity Index for Lupus) has emerged as an excellent predictor of LN activity as well as response to therapy, being able to predict efficacy within 3 months of therapy. If validated in additional large prospective studies, the RAIL biomarkers will transform the care of patients with LN, allowing for a personalized and predictive approach and improved outcomes.
狼疮性肾炎(LN)是一种常见且严重的表现,影响 60%的成人和 80%的系统性红斑狼疮儿童,多达 30%的患者进展为终末期肾病。目前仍然需要寻找非侵入性的疾病活动、损伤和治疗反应的标志物。此外,还需要能够预测治疗效果的非侵入性生物标志物,以便对新型药物进行具有成本效益的临床试验。
本综述探讨了尿蛋白质组学的方法学方面、蛋白质组谱分析在确定有前途的 LN 尿液生物标志物中的作用,以及将研究结果转化为 LN 管理中临床有用工具的情况。
有针对性和无偏性蛋白质组学已经确定了几种有前途的尿液生物标志物,可预测 LN 的活动、损伤(慢性)和对治疗的反应。特别是,一种称为 RAIL(狼疮肾炎活动指数)的生物学上合理的尿液生物标志物组合已经成为 LN 活动以及对治疗反应的优秀预测指标,能够在治疗 3 个月内预测疗效。如果在更多的大型前瞻性研究中得到验证,RAIL 生物标志物将改变 LN 患者的治疗方式,实现个性化和预测性的治疗方法,并改善预后。