Department of Internal Medicine, Seoul Veterans Hospital, Seoul, Korea.
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Lupus. 2021 Jul;30(8):1306-1313. doi: 10.1177/09612033211014268. Epub 2021 May 9.
The need for a biomarker with robust sensitivity and specificity in diagnosing systemic lupus erythematosus (SLE) remains unmet. Compared with blood samples, urine samples are more easily collected; thus, we aimed to identify such a biomarker based on urinary proteomics which could distinguish patients with SLE from healthy controls (HCs).
Urine samples were collected from 76 SLE patients who visited rheumatology clinic in 2019 at Asan medical center and from 25 HCs. Urine proteins were analyzed using sequential windowed acquisition of all theoretical fragment ion spectra-mass spectrometry, and the candidate marker was confirmed by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic curve analysis was used to determine the diagnostic value of the candidate biomarker.
Of 1157 proteins quantified, 153 were differentially expressed in urine samples from HCs. Among them were previously known markers including α-1-acid glycoprotein 1, α-2-HS-glycoprotein, ceruloplasmin, and prostaglandin-H2 D-isomerase. Moreover, the amount of β-2 glycoprotein (APOH) was increased in the urine of patients with SLE. The ELISA results also showed the level of urine APOH was higher in patients with SLE than in HCs and patients with rheumatoid arthritis. Moreover, the level was not different between SLE patients with and without nephritis. The urine APOH had an area under the curve value of 0.946 at a cut-off value of 228.53 ng/mg (sensitivity 91.5%, specificity 92.0%) for the diagnosis of SLE.
The results indicate that the urine APOH level can be an appropriate screening tool in a clinical setting when SLE is suspected.
目前仍需要一种具有高灵敏度和特异性的生物标志物来诊断系统性红斑狼疮（SLE）。与血液样本相比，尿液样本更容易采集；因此，我们旨在基于尿液蛋白质组学来寻找这样一种生物标志物，其能够将 SLE 患者与健康对照（HC）区分开来。
收集了 2019 年在亚洲医学中心风湿科就诊的 76 名 SLE 患者和 25 名 HC 的尿液样本。采用连续窗口采集所有理论碎片离子谱-质谱法分析尿液蛋白，并用酶联免疫吸附试验（ELISA）对候选标志物进行验证。采用受试者工作特征曲线分析来确定候选生物标志物的诊断价值。
在定量的 1157 种蛋白质中，有 153 种在 HC 的尿液样本中表达差异。其中包括先前已知的标志物，如α-1-酸性糖蛋白 1、α-2-HS-糖蛋白、铜蓝蛋白和前列腺素-H2 D-异构体。此外，SLE 患者尿液中的β-2 糖蛋白（APOH）含量增加。ELISA 结果还显示，SLE 患者的尿液 APOH 水平高于 HC 和类风湿关节炎患者，且肾炎患者与非肾炎患者的水平无差异。APOH 尿液的截断值为 228.53ng/mg 时，曲线下面积为 0.946（敏感性为 91.5%，特异性为 92.0%），可用于 SLE 的诊断。
结果表明，在怀疑 SLE 时，尿液 APOH 水平可作为一种合适的临床筛查工具。
