Renal Division, Peking University First Hospital, Beijing, China.
Institute of Nephrology, Peking University, Beijing, China.
Mediators Inflamm. 2023 Jul 28;2023:6107911. doi: 10.1155/2023/6107911. eCollection 2023.
Modified C-reactive protein (mCRP) is known to be involved in the upregulation and amplification of the local inflammatory response. This study investigated the circulating and local levels of mCRP and their relevance to clinicopathological features in patients with lupus nephritis.
Ninety-five patients with renal biopsy-proven lupus nephritis and 30 normal controls were enrolled in this study. Plasma and urinary mCRP were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of mCRP was detected by immunohistochemistry and immunofluorescence staining. A human proximal tubular epithelial cell line (HK2 cells) was incubated with purified IgG from lupus nephritis, and the production of CRP by HK2 cells was further evaluated.
Plasma and urinary levels of mCRP increased significantly in patients with lupus nephritis compared with normal controls ( = 0.013, < 0.001, respectively). The urinary mCRP levels were associated with interstitial inflammatory cell infiltration ( = 0.514, < 0.001) and interstitial fibrosis ( = 0.270, = 0.008). The ROC-AUC of the urinary mCRP levels for diagnosing tubulointerstitial lesions was 0.766. The urinary mCRP levels were closely associated with poor outcomes (HR: 1.204, 95% CI: 1.029-1.409, = 0.020). However, no correlations were found of the plasma mCRP levels with clinicopathological data or the prognosis of lupus nephritis. CRP was mostly deposited in the renal tubules in patients with lupus nephritis, and the expression of CRP was significantly correlated with tubulointerstitial lesion indices. Immunofluorescence staining showed that mCRP could colocalize with IgG in tubules. Lupus nephritis-derived IgG could induce CRP production by HK2 cells.
Urinary mCRP levels were significantly increased, and urinary mCRP might be a biomarker for tubulointerstitial lesions in patients with lupus nephritis. Renal CRP could be produced by tubular epithelial cells after stimulation by lupus nephritis-derived IgG, and the local presence of mCRP might play a critical role in the development of tubulointerstitial lesions.
已知改良 C 反应蛋白（mCRP）参与局部炎症反应的上调和放大。本研究探讨了狼疮肾炎患者循环和局部 mCRP 水平及其与临床病理特征的相关性。
本研究纳入了 95 例经肾活检证实的狼疮肾炎患者和 30 名正常对照者。通过酶联免疫吸附试验（ELISA）检测血浆和尿液中的 mCRP。通过免疫组化和免疫荧光染色检测 mCRP 在肾脏中的沉积。将纯化的狼疮肾炎 IgG 孵育于人近端肾小管上皮细胞系（HK2 细胞），进一步评估 HK2 细胞中 CRP 的产生。
与正常对照组相比，狼疮肾炎患者的血浆和尿液 mCRP 水平显著升高（=0.013，<0.001）。尿 mCRP 水平与间质炎症细胞浸润（=0.514，<0.001）和间质纤维化（=0.270，=0.008）相关。尿 mCRP 水平诊断肾小管间质病变的 ROC-AUC 为 0.766。尿 mCRP 水平与不良结局密切相关（HR：1.204，95%CI：1.029-1.409，=0.020）。然而，血浆 mCRP 水平与临床病理数据或狼疮肾炎的预后均无相关性。CRP 主要沉积在狼疮肾炎患者的肾小管中，CRP 的表达与肾小管间质病变指数显著相关。免疫荧光染色显示 mCRP 可与小管中的 IgG 共定位。狼疮肾炎衍生的 IgG 可诱导 HK2 细胞产生 CRP。
尿 mCRP 水平显著升高，尿 mCRP 可能是狼疮肾炎患者肾小管间质病变的生物标志物。狼疮肾炎衍生的 IgG 可刺激肾小管上皮细胞产生 CRP，局部 mCRP 的存在可能在肾小管间质病变的发生中起关键作用。
