Shoctor Nicholas A, Brady Makayla P, Lightman Rebecca R, Overton Kristen N, Tandon Shweta, Mathis Steven P, Rane Madhavi J, Barati Michelle T, Arriens Cristina G, Powell David W, Caster Dawn J
Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA.
Glomerular Dis. 2025 Jun 24;5(1):328-343. doi: 10.1159/000547044. eCollection 2025 Jan-Dec.
Lupus nephritis (LN) is kidney inflammation that commonly occurs from systemic lupus erythematosus. NF-κB activity is increased in LN patients, leading to elevated circulating concentrations of immune modulators that contribute to LN pathophysiology. This study sought to investigate this phenomenon with the aim of discovering novel serum biomarkers for LN.
A multiplex antibody-based assay was performed with serum from 24 LN patients and 7 healthy controls (HCs) to determine if 48 NF-κB-regulated proteins were elevated in LN patients. Confirmation ELISAs were performed on stem cell factor (SCF), macrophage colony-stimulating factor (M-CSF), and interleukin-2 receptor alpha (IL-2Rα) subunit in a separate sample cohort of 27 LN patients and 10 HC. Follow-up ELISAs were performed on samples obtained from the same patients during LN remission to determine if these candidates were reliable predictors of disease activity. Comparisons of protein levels between LN patients and HC were performed using a series of 2-tailed Mann-Whitney tests. Paired samples were analyzed using a Wilcoxon matched pairs test. Two-tailed Spearman's correlation analyses were used to compare serum protein concentrations with LN clinical parameters. All values were adjusted for multiple comparisons.
SCF, M-CSF, and IL-2Rα were significantly elevated in LN serum. Elevated serum SCF and M-CSF were significantly correlated with elevated urine protein to creatinine ratio, decreased estimated glomerular filtration rate, and elevated serum creatinine. Elevated serum IL-2Rα was significantly correlated with elevated serum creatinine. Serum SCF concentration was significantly decreased during LN remission in paired samples from individuals, but it was not a good predictor at the population level (AUC = 0.6265).
We identified the NF-κB-regulated proteins SCF, M-CSF, and IL-2Rα as candidate serum biomarkers for consideration in monitoring LN activity. Our findings also indicate the importance for follow-up mechanistic studies pertaining to these inflammatory mediators.
狼疮性肾炎（LN）是一种常见于系统性红斑狼疮的肾脏炎症。LN患者体内的核因子κB（NF-κB）活性增强，导致循环中免疫调节因子浓度升高，这对LN的病理生理过程有影响。本研究旨在调查这一现象，以期发现LN的新型血清生物标志物。
采用基于多重抗体的检测方法，对24例LN患者和7例健康对照（HC）的血清进行检测，以确定48种NF-κB调节蛋白在LN患者中是否升高。在一个由27例LN患者和10例HC组成的独立样本队列中，对干细胞因子（SCF）、巨噬细胞集落刺激因子（M-CSF）和白细胞介素-2受体α（IL-2Rα）亚基进行确认性酶联免疫吸附测定（ELISA）。对同一患者在LN缓解期采集的样本进行随访ELISA检测，以确定这些候选物是否为疾病活动的可靠预测指标。使用一系列双尾曼-惠特尼检验对LN患者和HC之间的蛋白质水平进行比较。配对样本采用威尔科克森配对检验进行分析。采用双尾斯皮尔曼相关性分析比较血清蛋白浓度与LN临床参数。所有P值均针对多重比较进行调整。
LN血清中SCF、M-CSF和IL-2Rα显著升高。血清SCF和M-CSF升高与尿蛋白肌酐比值升高、估计肾小球滤过率降低和血清肌酐升高显著相关。血清IL-2Rα升高与血清肌酐升高显著相关。个体配对样本中，LN缓解期血清SCF浓度显著降低，但在群体水平上它不是一个良好的预测指标（曲线下面积[AUC]=0.6265）。
我们确定NF-κB调节蛋白SCF、M-CSF和IL-2Rα为监测LN活动时可供考虑的候选血清生物标志物。我们的研究结果还表明了对这些炎症介质进行后续机制研究的重要性。
