Departmento de Biología Experimental, Universidad de Jaén, Spain.
Departmento de Biología Celular, Universidad de Granada, Spain.
J Proteomics. 2018 Aug 30;186:47-55. doi: 10.1016/j.jprot.2018.07.009. Epub 2018 Jul 17.
Fibromyalgia (FM) is a form of non-articular rheumatism difficult to diagnose and treat because its etiology remains still elusive. Proteomics makes possible the systematic analysis of hundreds of proteins in clinical samples. Consequently, it has become a key tool for finding altered molecular pathways in different diseases. In this context, the present study analyzes changes in the plasma proteome of patients with FM by nanoscale liquid chromatography coupled to tandem mass spectrometry. Deregulated proteins were studied using Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes. Conventional analytical methods were used to validate selected proteins. We found a total of 33 proteins differentially expressed in patients with FM. Haptoglobin and fibrinogen showed the highest FM/control ratio. IPA analysis revealed that the top enriched canonical pathways were acute-phase response signaling, Liver-X Receptor/Retinoid-X Receptor activation, Farnesoid-X Receptor/Retinoid-X Receptor activation, and coagulation and complement systems. The importance of inflammation in FM was corroborated by the increase in erythrocyte sedimentation rate. In conclusion, our results support the existence of a plasma protein signature of FM that involves different biological pathways all of them related to inflammation, and point to haptoglobin and fibrinogen as plausible biomarker-candidates for future studies.
The etiology of fibromyalgia (FM) remains elusive making its diagnosis and treatment difficult. The characterization of the proteome signature of this syndrome will improve its understanding. However, to date proteomic analyses in FM are scarce. The goal of the present work is to analyse, for the first time, changes in plasma protein profiles of patients with FM in comparison to control subjects, using label free relative protein quantification by nanoscale liquid chromatography coupled to tandem mass spectrometry. Our data demonstrate the existence of a common protein signature in the plasma of patients with FM that could explain some of the symptoms associated to this syndrome. The analysis of the 33 proteins differentially expressed corroborates the crucial role of inflammation in the pathogenesis of this syndrome. The interplay of the complement and coagulation cascades contributes to the inflammatory process, while the activation of Liver-X Receptor/Retinoid-X Receptor and Farnesoid-X Receptor/Retinoid-X Receptor could attempt to alleviate it. Finally, we have identified two proteins, haptoglobin and fibrinogen, as potential biomarker-candidates of FM for future studies.
纤维肌痛 (FM) 是一种非关节性风湿病，由于其病因仍难以捉摸，因此难以诊断和治疗。蛋白质组学使得对临床样本中的数百种蛋白质进行系统分析成为可能。因此，它已成为寻找不同疾病中改变的分子途径的关键工具。在这种情况下，本研究通过纳米液相色谱与串联质谱联用分析了纤维肌痛患者血浆蛋白质组的变化。使用 IPA（Ingenuity Pathways Analysis）和京都基因与基因组百科全书对失调蛋白进行了研究。使用常规分析方法验证了选定的蛋白质。我们发现纤维肌痛患者的 33 种蛋白质表达存在差异。触珠蛋白和纤维蛋白原显示出最高的纤维肌痛/对照比值。IPA 分析显示，最富集的经典途径是急性期反应信号、肝 X 受体/视黄酸受体激活、法尼醇 X 受体/视黄酸受体激活以及凝血和补体系统。红细胞沉降率的增加证实了炎症在纤维肌痛中的重要性。总之，我们的结果支持存在纤维肌痛的血浆蛋白质特征，该特征涉及到不同的生物学途径，所有这些途径都与炎症有关，并指出触珠蛋白和纤维蛋白原可能是未来研究的生物标志物候选物。
纤维肌痛 (FM) 的病因仍难以捉摸，使其诊断和治疗变得困难。对该综合征蛋白质组特征的描述将提高对其的认识。然而，迄今为止，纤维肌痛的蛋白质组分析很少。本工作的目的是首次使用纳米液相色谱与串联质谱联用的无标签相对蛋白质定量分析，分析纤维肌痛患者与对照相比血浆蛋白谱的变化。我们的数据表明，纤维肌痛患者血浆中存在共同的蛋白质特征，这可以解释与该综合征相关的一些症状。对 33 种差异表达蛋白的分析证实了炎症在该综合征发病机制中的关键作用。补体和凝血级联的相互作用有助于炎症过程，而肝 X 受体/视黄酸受体和法尼醇 X 受体/视黄酸受体的激活可能试图缓解炎症。最后，我们确定了两种蛋白质，触珠蛋白和纤维蛋白原，作为纤维肌痛未来研究的潜在生物标志物候选物。
