Department of Biomedical Engineering, University of Houston , Houston, Texas, USA.
Expert Rev Proteomics. 2020 Oct;17(10):767-776. doi: 10.1080/14789450.2020.1874356. Epub 2021 Jan 19.
Proteomic approaches are central in biomarker discovery. While mass-spectrometry-based techniques are widely used, novel targeted proteomic platforms have enabled the high-throughput detection of low-abundance proteins in an affinity-based manner. Urine has gained growing attention as an ideal biofluid for monitoring renal disease including lupus nephritis (LN).
Pubmed was screened for targeted proteomic studies of LN urine interrogating ≥1000 proteins. Data from the primary studies were combined and a meta-analysis was performed. Shared proteins elevated in active LN across studies were identified, and relevant pathways were elucidated using ingenuity pathway and gene ontology analysis. Urine proteomic data was cross-referenced against renal single-cell RNAseq data from LN kidneys.
Two high-throughput targeted proteomic platforms with capacity to interrogate ≥1000 proteins have been used to investigate LN urine. Twenty-three urine proteins were significantly elevated in both studies, including 10 chemokines, and proteins implicated in angiogenesis, and extracellular matrix turnover. Of these, Cathepsin S, CXCL10, FasL, ferritin, macrophage migration inhibitory factor (MIF), and resistin were also significantly elevated within LN kidneys.
Targeted urinary proteomics have uncovered multiple novel biomarkers for LN. Further validation in prospective cohorts and mechanistic studies are warranted to establish their clinical utility.
蛋白质组学方法是生物标志物发现的核心。虽然基于质谱的技术被广泛应用，但新型靶向蛋白质组学平台已能够以亲和为基础的方式高通量检测低丰度蛋白质。尿液作为监测包括狼疮肾炎（LN）在内的肾脏疾病的理想生物液体受到了越来越多的关注。
在 Pubmed 上筛选了针对 LN 尿液进行的靶向蛋白质组学研究，这些研究询问了≥1000 种蛋白质。对主要研究的数据进行了合并，并进行了荟萃分析。鉴定了在活跃的 LN 中在所有研究中升高的共享蛋白质，并使用 Ingenuity 通路和基因本体分析阐明了相关途径。将尿液蛋白质组学数据与 LN 肾脏的单细胞 RNAseq 数据进行交叉引用。
两种具有≥1000 种蛋白质检测能力的高通量靶向蛋白质组学平台已被用于研究 LN 尿液。两项研究均发现 23 种尿液蛋白质显著升高，包括 10 种趋化因子，以及与血管生成和细胞外基质周转有关的蛋白质。其中，组织蛋白酶 S、CXCL10、FasL、铁蛋白、迁移抑制因子（MIF）和抵抗素在 LN 肾脏中也显著升高。
靶向尿液蛋白质组学已经发现了多个用于 LN 的新型生物标志物。需要进一步在前瞻性队列和机制研究中进行验证，以确定它们的临床应用价值。
