Zhong Lijun, Liu Jiao, Zhou Juntuo, Sun Lin, Li Changhong, Li Xinyi, Liu Rui, Zhao Jinxia, Yang Bin, Liu Xiangyuan, Deng Xiaoli
Medical and Health Analytical Center, Peking University Health Science Center Beijing, China.
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center Beijing, China.
Int J Clin Exp Pathol. 2017 Oct 1;10(10):10681-10694. eCollection 2017.
Systemic lupus erythematosus (SLE) is an autoimmune disease which is characterized by the presence of autoantibodies. It will be helpful if specific serum biomarkers can be used for monitoring the disease activity as well as differentiating SLE from other diseases. For this purpose, we used a label free-based two dimensional liquid chromatography mass spectrometry platform to analyze serum samples from SLE patients in active or inactivestage. Significant differences were found for 42 serum proteins implicated in pathways including complement and coagulation cascades. Further gene set enrichment analysis revealed that gene sets including formation of fibrin clot, ECM glycoproteins and innate immune system were highly correlated with the SLE disease activity. To further assess the validity of these findings, thrombospondin-4 was selected for subsequent ELISA assays. We also explored the autoantibody of three candidate biomarkers in larger cohorts including SLE, Rheumatoid arthritis, Sjogrensyndrome patients and normal controls. Our findings provided valuable information on the proteomic changes in the serum of different SLE disease activity. Serum properdin, collectin-11 and thrombospondin-4 were valuable in monitoring the disease activity of SLE, and the autoantibodies to them may be valuable in differentiating SLE from other diseases for clinical diagnosis in the future.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是存在自身抗体。如果能够使用特定的血清生物标志物来监测疾病活动以及将SLE与其他疾病区分开来，将会很有帮助。为此，我们使用了基于无标记的二维液相色谱质谱平台来分析处于活动期或非活动期的SLE患者的血清样本。在涉及补体和凝血级联等途径的42种血清蛋白中发现了显著差异。进一步的基因集富集分析表明，包括纤维蛋白凝块形成、细胞外基质糖蛋白和先天免疫系统在内的基因集与SLE疾病活动高度相关。为了进一步评估这些发现的有效性，选择血小板反应蛋白-4进行后续的酶联免疫吸附测定（ELISA）。我们还在包括SLE、类风湿性关节炎、干燥综合征患者和正常对照的更大队列中探索了三种候选生物标志物的自身抗体。我们的发现为不同SLE疾病活动状态下血清中的蛋白质组变化提供了有价值的信息。血清备解素、凝集素-11和血小板反应蛋白-4在监测SLE疾病活动方面具有价值，并且针对它们的自身抗体在未来临床诊断中区分SLE与其他疾病方面可能具有价值。
