Hou Xiaodie, Zhang Yuhang, Yang Wei, Zou Guanglan, Liu Yong
Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan; and Precision Pathology Diagnosis for Serious Diseases Key Laboratory of Luzhou, Luzhou, Sichuan, China.
Clin Exp Rheumatol. 2025 Jul;43(7):1245-1251. doi: 10.55563/clinexprheumatol/jzt8sp. Epub 2025 Mar 28.
Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) that involves the kidneys and severely affects renal function or even leads to renal failure. The aim of this study was to quantify the expressions of nuclear factor kappa B (NF-κ B) and heat shock protein 90 (HSP90) in patients with LN and investigate the pathological mechanisms involved.
We collected fifty-two renal needle biopsy tissues and complete clinical data from patients diagnosed with LN. We also selected thirty-two renal specimens from hydronephrosis surgery and autopsy served as the control group. The expressions of NF-κ B and HSP90 in kidney histology were detected. In addition, we collected Fasting peripheral venous blood samples from 16 patients with SLE, 12 patients with LN, and 16 healthy controls diagnosed in our hospital. And the gene expression levels of NF-κ B and HSP90 in peripheral blood mononuclear cells (PBMCs) of the subjects were determined.
The expression levels of NF-κ B and HSP90 in kidney histology of patients with LN were significantly higher than those in the control group. High NF-κ B and HSP90 protein expressions were associated with severe LN activity (SLEDAI >15 points) (p<0.05). Compared with the control group, the expression levels of NF-κ B and HSP90 mRNA were significantly up regulated in PBMCs of the SLE patient group (p<0.05). Moreover, the expression levels of NF-κ B and HSP90 mRNA in PBMCs were significantly up regulated in the LN patient group compared with the SLE patient group (p<0.05). In addition, the levels of NF-κ B and HSP90 mRNA expression in PBMCs of the LN patient group were positively correlated (p<0.05). The area under the receiver operating characteristic (ROC) curve for NF-κ B mRNA expression in PBMCs from patients with LN to diagnose SLE kidney damage was 0.929 (95% confidence interval [CI] 0.833-1.000, p<0.001), and the AUC for HSP90 mRNA expression was 0.742 (95% CI 0.556-0.927, p<0.05).
NF-κ B and HSP90 may play a synergistic role in the pathogenesis of LN. Their elevated expression has a high diagnostic accuracy for LN or SLE without renal damage. Hence, NF-κ B and HSP90 can be used as therapeutic targets and biomarkers for the diagnosis of LN.
狼疮性肾炎（LN）是系统性红斑狼疮（SLE）的常见并发症，累及肾脏，严重影响肾功能，甚至导致肾衰竭。本研究旨在量化LN患者中核因子κB（NF-κB）和热休克蛋白90（HSP90）的表达，并探讨其病理机制。
我们收集了52例经诊断为LN患者的肾穿刺活检组织及完整临床资料。我们还选取了32例肾盂积水手术及尸检的肾标本作为对照组。检测肾脏组织学中NF-κB和HSP90的表达。此外，我们收集了我院诊断的16例SLE患者、12例LN患者及16例健康对照者的空腹外周静脉血样本。并测定受试者外周血单个核细胞（PBMC）中NF-κB和HSP90的基因表达水平。
LN患者肾脏组织学中NF-κB和HSP90的表达水平显著高于对照组。高NF-κB和HSP90蛋白表达与严重的LN活动（SLEDAI>15分）相关（p<0.05）。与对照组相比，SLE患者组PBMC中NF-κB和HSP90 mRNA的表达水平显著上调（p<0.05）。此外，与SLE患者组相比，LN患者组PBMC中NF-κB和HSP90 mRNA的表达水平显著上调（p<0.05）。此外，LN患者组PBMC中NF-κB和HSP90 mRNA表达水平呈正相关（p<0.05）。LN患者PBMC中NF-κB mRNA表达诊断SLE肾损伤的受试者工作特征（ROC）曲线下面积为0.929（95%置信区间[CI]0.833 - 1.000，p<0.001），HSP90 mRNA表达的AUC为0.742（95%CI 0.556 - 0.927，p<0.05）。
NF-κB和HSP90可能在LN发病机制中起协同作用。它们的表达升高对LN或无肾损伤的SLE具有较高的诊断准确性。因此，NF-κB和HSP90可作为LN诊断的治疗靶点和生物标志物。
