尿液 SERPINC1/ORM1 作为 MRL-lpr 小鼠狼疮肾炎早期检测的生物标志物。
Urine SERPINC1/ORM1 as biomarkers for early detection of lupus nephritis in MRL-lpr mice.
机构信息
Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Convergence Medicine Research Center, Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
出版信息
Front Immunol. 2023 Sep 8;14:1148574. doi: 10.3389/fimmu.2023.1148574. eCollection 2023.
BACKGROUND
To evaluate the usefulness of urine SERPINC1 and ORM1 as biomarkers for early detection of lupus nephritis (LN).
METHODS
Using proteomics, we screened for potential urine biomarkers that differentiate LN from systemic lupus erythematosus (SLE) patients without nephritis. In addition, urine levels of target biomarkers were measured by ELISA in 13- and 23-week-old MRL-lpr (murine model for LN) and MRL/MpJ mice. Histological analysis was also performed on the kidneys of 23-week-old mice.
RESULTS
Urine SERPINC1 and ORM1 were elevated in SLE patients with newly diagnosed LN compared with SLE patients without LN (SERPINC1, AUC=.892, P<.001; ORM1, AUC=.886, P<.001). Levels of urine SERPINC1 and ORM1 were also significantly higher in MRL-lpr mice than in MRL/MpJ mice at 13 and 23 weeks (SERPINC1: p<.01 and p<.001 at 13 and 23 weeks, respectively; ORM1: p<.01 at 13 and 23 weeks). In contrast, a significant difference in urine albumin between the two groups was only observed at 23 weeks (p<.001) not at 13 weeks (p=.83). Regarding the kidney pathology of MPL-lpr mice, urine ORM1 and urine albumin, but not urine SERPINC1, were positively correlated with the activity index (ORM1, rho =.879, p<.001; albumin, rho =.807, p=.003) and chronicity index (ORM1, rho =.947, p<.001; albumin, rho =.869, p<.001).
CONCLUSION
We propose that urine SERPINC1 and ORM1 are novel biomarkers for early LN.
背景
评估尿 SERPINC1 和 ORM1 作为狼疮肾炎 (LN) 早期检测生物标志物的有用性。
方法
使用蛋白质组学，我们筛选出潜在的尿生物标志物，以区分 LN 与无肾炎的系统性红斑狼疮 (SLE) 患者。此外，通过 ELISA 测量了 13 周和 23 周龄 MRL-lpr（LN 的小鼠模型）和 MRL/MpJ 小鼠的目标生物标志物的尿水平。还对 23 周龄小鼠的肾脏进行了组织学分析。
结果
与无 LN 的 SLE 患者相比，新诊断为 LN 的 SLE 患者的尿 SERPINC1 和 ORM1 升高（SERPINC1，AUC=.892，P<.001；ORM1，AUC=.886，P<.001）。在 13 周和 23 周时，MRL-lpr 小鼠的尿 SERPINC1 和 ORM1 水平也明显高于 MRL/MpJ 小鼠（SERPINC1：分别在 13 周和 23 周时 p<.01 和 p<.001；ORM1：在 13 周和 23 周时 p<.01）。相比之下，两组之间尿白蛋白的差异仅在 23 周时观察到（p<.001），而在 13 周时没有（p=.83）。关于 MPL-lpr 小鼠的肾脏病理学，尿 ORM1 和尿白蛋白，但不是尿 SERPINC1，与活动指数呈正相关（ORM1，rho=.879，p<.001；白蛋白，rho=.807，p=.003）和慢性指数（ORM1，rho=.947，p<.001；白蛋白，rho=.869，p<.001）。
结论
我们提出尿 SERPINC1 和 ORM1 是早期 LN 的新型生物标志物。
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