Tang Chenling, Teymur Aygun, Wu Tianfu
Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA.
Diagnostics (Basel). 2024 Dec 12;14(24):2787. doi: 10.3390/diagnostics14242787.
BACKGROUND/OBJECTIVES: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), involving immune complex deposition in the kidneys. While renal biopsy is the diagnostic gold standard, its invasiveness limits frequent use, driving the need for non-invasive urinary biomarkers to monitor disease progression and response to treatment. This study aimed to identify and validate urinary biomarkers for LN.
Data from 10 LN-related omics databases, including urine, PBMCs, and kidney tissue, were analyzed. Differentially expressed proteins (DEPs) and genes (DEGs) were identified, and candidate biomarkers were validated via ELISA in an independent cohort of 87 urine samples.
We identified 78 biomarkers, with 14 overlapping across transcriptomic categories. Novel urinary biomarkers, including SERPING1, SLPI, and CD48, were validated. Urinary CD163, VCAM1, and ALCAM levels showed significant differences between LN and healthy controls, while urinary immune complexes (ICx) demonstrated superior diagnostic performance, with urinary ALCAM-ICx and CCL21-ICx achieving the highest AUC values.
Our findings highlight the potential of urinary immune complexes and antigens as non-invasive biomarkers for LN. ALCAM, CD163, and SERPING1-ICx, in particular, were found as promising candidates for a urinary biomarker panel to aid in the diagnosis and monitoring of LN.
背景/目的：狼疮性肾炎（LN）是系统性红斑狼疮（SLE）的一种严重并发症，涉及免疫复合物在肾脏中的沉积。虽然肾活检是诊断的金标准，但其侵入性限制了其频繁使用，从而推动了对非侵入性尿液生物标志物的需求，以监测疾病进展和对治疗的反应。本研究旨在识别和验证LN的尿液生物标志物。
分析了来自10个与LN相关的组学数据库的数据，包括尿液、外周血单核细胞（PBMC）和肾组织。识别差异表达蛋白（DEP）和基因（DEG），并通过酶联免疫吸附测定（ELISA）在一个由87个尿液样本组成的独立队列中验证候选生物标志物。
我们识别出78种生物标志物，其中14种在转录组类别中重叠。包括丝氨酸蛋白酶抑制剂C1（SERPING1）、分泌型白细胞蛋白酶抑制剂（SLPI）和CD48在内的新型尿液生物标志物得到了验证。LN患者与健康对照者的尿液中CD163、血管细胞黏附分子1（VCAM1）和活化白细胞黏附分子（ALCAM）水平存在显著差异，而尿液免疫复合物（ICx）表现出卓越的诊断性能，尿液中的ALCAM-ICx和CC趋化因子配体21（CCL21）-ICx的曲线下面积（AUC）值最高。
我们的研究结果突出了尿液免疫复合物和抗原作为LN非侵入性生物标志物的潜力。特别是，发现ALCAM、CD163和SERPING1-ICx是用于辅助LN诊断和监测的尿液生物标志物组合的有前景的候选物。
