Proteomic analyses reveal cystatin c is a promising biomarker for evaluation of systemic lupus erythematosus.

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Clinical proteomics Pub Date : 2023-10-18 DOI:10.1186/s12014-023-09434-9

He Huang, Yukun Zhang, Lan Gui, Li Zhang, Minglong Cai, Yujun Sheng

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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蛋白质组学分析显示胱抑素c是一种很有前途的评估系统性红斑狼疮的生物标志物。

背景：系统性红斑狼疮（SLE）是一种自身免疫性疾病，涉及多个器官，尤其是肾脏。然而，潜在的机制仍不清楚，准确的生物标志物仍然缺乏。本研究旨在使用定量蛋白质组学鉴定生物标志物，以评估SLE患者的器官损伤和疾病活动。方法：应用质谱法对15例SLE患者和15例年龄匹配的健康对照进行蛋白质组学分析。比较了四种主要亚型的蛋白质组学特征：SLE伴蛋白尿（SLE-PN）、SLE无蛋白尿（SLE非PN）、抗dsDNA阳性的SLE（SLE-DP）和抗dsDNA阴性的SLE（SLE非DP）。基因本体生物学过程分析揭示了差异表达的蛋白质网络。采用免疫比浊法测定了200例SLE患者的半胱氨酸蛋白酶抑制剂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。结果：蛋白质组学分析显示，SLE-PN和SLE-DP组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、补体C3水平降低和SLE疾病活动指数评分的相关性在一个大型独立队列中得到了进一步验证。结论：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一个有前途的标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical proteomics BIOCHEMICAL RESEARCH METHODS-

CiteScore

5.80

自引率

2.60%

发文量

审稿时长

17 weeks

期刊介绍： Clinical Proteomics encompasses all aspects of translational proteomics. Special emphasis will be placed on the application of proteomic technology to all aspects of clinical research and molecular medicine. The journal is committed to rapid scientific review and timely publication of submitted manuscripts.