Abstract

Behçet’s syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Investigation of proteome profiles of disease specific cells facilitates our understanding of the processes and related molecular pathways, especially in disorders like BS with complex inheritance pattern and clinical heterogeneity. In the current study, we evaluated the peripheral blood mononuclear cells (PBMCs) proteome of 59 patients with BS (33 in active and 26 in inactive phases) and of 28 healthy controls using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Differentially expressed protein spots with at least twofold and/or statistically significant change (p ≤ 0.05) between active BS vs inactive BS, and also active BS vs healthy controls were identified by mass spectrometry (MALDI-TOF/TOF). Bioinformatic analyses revealed 16 differentially expressed proteins (12 of them in active vs inactive BS comparison, whereas 11 of them for active BS vs healthy control comparison) belonging to glycolysis, cytoskeleton organization, protein folding, and regulation of blood coagulation pathways. Stathmin (active BS vs inactive BS; fourfold, active BS vs healthy control; 4.7-fold) and WD repeat-containing protein-1 (active BS vs inactive BS; 2.7-fold, active BS vs healthy control; 2.7-fold), which are cytoskeleton-related proteins, were found to be lower in active patients compared to inactive patients and healthy control. Decreased levels of calreticulin (active BS vs inactive BS; 1.29-fold) and heat shock 70 kDa protein 8 (active BS vs healthy control; 1.5-fold) which are involved in protein folding and endoplasmic reticulum (ER) stress process, were observed in patients with active phase of BS. Down-regulation of protein folding and ER stress process proteins in BS patients may further support the involvement of ER stress in BS.

中文翻译：

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Behçet综合征的外周血单核细胞蛋白质组概况

摘要

Behçet综合征（BS）是一种病因不明的全身性炎症性疾病。对疾病特异性细胞的蛋白质组图谱的研究有助于我们了解其过程和相关的分子途径，尤其是在诸如具有复杂遗传模式和临床异质性的BS等疾病中。在本研究中，我们使用二维荧光差值凝胶电泳（2D-DIGE）评估了59例BS患者（活跃期33例，无效期26例）和28位健康对照的外周血单个核细胞（PBMC）蛋白质组。差异表达的蛋白质斑点具有至少两倍和/或统计学上显着的变化（p 质谱（MALDI-TOF / TOF）可以确定活跃BS与未活跃BS之间的差异（≤0.05），以及活跃BS与健康对照组之间的差异。生物信息学分析揭示了16种差异表达的蛋白（其中有12种在活性BS与无活性BS比较中，而有11种在活性BS与健康对照中比较）属于糖酵解，细胞骨架组织，蛋白质折叠和血液凝固途径的调节。Stathmin（活跃BS相对于非活跃BS;四倍，活跃BS相对于健康对照组; 4.7倍）和WD重复序列蛋白1（活跃BS相对于非活跃BS; 2.7倍，活跃BS相对于健康对照组; 2.7倍）与无活动的患者和健康对照相比，活动患者的细胞骨架相关蛋白含量较低。钙网蛋白水平降低（活动BS与不活动BS; 1。在BS活跃期患者中观察到29倍）和热休克70 kDa蛋白8（活性BS相对健康对照组； 1.5倍）参与蛋白质折叠和内质网（ER）应激过程。BS患者中蛋白质折叠和ER应激过程蛋白的下调可能进一步支持ER应激参与BS。