Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still's Disease.
Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still's Disease.
复制标题
尿液蛋白质组学鉴定用于诊断成人斯蒂尔病的新型生物标志物
DOI：
10.3389/fimmu.2020.02112
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发表时间：
2020
影响因子：
7.3
通讯作者：
Ye J
中科院分区：
文献类型：
--
作者：
Sun Y;Wang F;Zhou Z;Teng J;Su Y;Chi H;Wang Z;Hu Q;Jia J;Liu T;Liu H;Cheng X;Shi H;Tan Y;Yang C;Ye J
成人斯蒂尔病（AOSD）是一种全身性、多基因自身炎症性疾病，诊断AOSD必须排除肿瘤、感染和其他自身免疫性疾病。发展一种快速、有效、无创的诊断方法是改善AOSD治疗的迫切需要。在这项研究中，我们首先进行了尿蛋白质组学研究，使用同量异位素标签的相对和绝对定量（iTRAQ）标记结合液相色谱-串联质谱分析与AOSD患者和健康对照（HC）受试者。尿蛋白在先天免疫系统和中性粒细胞脱颗粒途径中富集，我们确定α-1-酸性糖蛋白1（LRG 1）、乳清类粘蛋白1（ORM 1）和ORM 2蛋白在AOSD患者中高度表达。通过酶联免疫吸附试验，在活动性AOSD患者、疾病对照和HC受试者中进一步验证了LRG 1、ORM 1和ORM 2的尿液水平升高。受试者工作特征曲线显示，LRG 1、ORM 1和ORM 2的曲线下面积分别为0.700、0.837和0.736（均p < 0.05）。此外，我们还发现尿液中LRG 1、ORM 1和ORM 2的水平与系统评分和红细胞沉降率呈正相关，尿液中LRG 1的水平与白细胞介素1β（IL-1β）、IL-6和IL-18的水平呈正相关，而尿液中ORM 1的水平与IL-1β的水平呈正相关。总之，我们的研究确定了新的尿液标记物，用于非侵入性和简单的AOSD筛查。
Adult-onset Still’s disease (AOSD) is a systemic, multigenic autoinflammatory disease, and the diagnosis of AOSD must rule out neoplasms, infections, and other autoimmune diseases. Development of a rapid and efficient but non-invasive diagnosis method is urgently needed for improving AOSD therapy. In this study, we first performed a urinary proteomic study using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography–tandem mass spectrometry analysis in patients with AOSD and healthy control (HC) subjects. The urinary proteins were enriched in pathways of the innate immune system and neutrophil degranulation, and we identified that the α-1-acid glycoprotein 1 (LRG1), orosomucoid 1 (ORM1), and ORM2 proteins were highly expressed in patients with AOSD. The elevated urine levels of LRG1, ORM1, and ORM2 were further validated by enzyme-linked immunosorbent assay in active patients with AOSD, disease controls, and HC subjects. Receiver operating characteristic curves showed that the areas under the curve of LRG1, ORM1, and ORM2 were 0.700, 0.837, and 0.736, respectively (all p < 0.05). Furthermore, we found that the urine levels of LRG1, ORM1, and ORM2 were positively correlated with the systemic score and erythrocyte sedimentation rate and that the urine levels of LRG1 were positively correlated with interleukin 1β (IL-1β), IL-6, and IL-18 levels, whereas the urine levels of ORM1 were positively correlated with the IL-1β level. Together, our study identified novel urinary markers for non-invasive and simple screening of AOSD.