Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement, especially the kidneys. However, the underlying mechanism remains unclear, and accurate biomarkers are still lacking. This study aimed to identify biomarkers to assess organ damage and disease activity in patients with SLE using quantitative proteomics. Proteomic analysis was performed using mass spectrometry in 15 patients with SLE and 15 age-matched healthy controls. Proteomic profiles were compared in four main subtypes: SLE with proteinuria (SLE-PN), SLE without proteinuria (SLE-non-PN), SLE with anti-dsDNA positivity (SLE-DP), and SLE with anti-dsDNA negativity (SLE-non-DP). Gene ontology biological process analysis revealed differentially expressed protein networks. Cystatin C (CysC) levels were measured in 200 patients with SLE using an immunoturbidimetric assay. Clinical and laboratory data were collected to assess their correlation with serum CysC levels. Proteomic analysis showed that upregulated proteins in both the SLE-PN and SLE-DP groups were mainly mapped to neutrophil activation networks. Moreover, CysC from neutrophil activation networks was upregulated in both the SLE-PN and SLE-DP groups. The associations of serum CysC level with proteinuria, anti-dsDNA positivity, lower complement C3 levels, and SLE disease activity index score in patients with SLE were further validated in a large independent cohort. Neutrophil activation is more prominent in SLE with proteinuria and anti-dsDNA positivity, and CysC is a promising marker for monitoring organ damage and disease activity in SLE.

中文翻译：

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蛋白质组学分析表明胱抑素 C 是评估系统性红斑狼疮的一种有前途的生物标志物

系统性红斑狼疮（SLE）是一种累及多个器官的自身免疫性疾病，尤其是肾脏。然而，其潜在机制仍不清楚，并且仍然缺乏准确的生物标志物。本研究旨在利用定量蛋白质组学鉴定生物标志物来评估 SLE 患者的器官损伤和疾病活动性。使用质谱法对 15 名 SLE 患者和 15 名年龄匹配的健康对照者进行蛋白质组分析。比较了四种主要亚型的蛋白质组谱：伴蛋白尿的 SLE (SLE-PN)、不伴蛋白尿的 SLE (SLE-non-PN)、伴抗 dsDNA 阳性的 SLE (SLE-DP) 和伴抗 dsDNA 阴性的 SLE (SLE) -非DP）。基因本体生物过程分析揭示了差异表达的蛋白质网络。使用免疫比浊法测量了 200 名 SLE 患者的胱抑素 C (CysC) 水平。收集临床和实验室数据以评估其与血清 CysC 水平的相关性。蛋白质组学分析表明，SLE-PN 和 SLE-DP 组中上调的蛋白质主要定位于中性粒细胞激活网络。此外，来自中性粒细胞激活网络的 CysC 在 SLE-PN 和 SLE-DP 组中均上调。SLE 患者血清 CysC 水平与蛋白尿、抗 dsDNA 阳性、较低补体 C3 水平和 SLE 疾病活动指数评分的关联在大型独立队列中得到进一步验证。中性粒细胞活化在伴有蛋白尿和抗 dsDNA 阳性的 SLE 中更为突出，CysC 是监测 SLE 器官损伤和疾病活动的有前景的标记物。