Protein profiles of peripheral blood mononuclear cells as a candidate biomarker for Behçet's disease.

Protein profiles of peripheral blood mononuclear cells as a candidate biomarker for Behçet's disease.
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DOI:
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发表时间:
2014-07
影响因子:
3.7
通讯作者:
T. Yoshioka;M. Kurokawa;Toshiyuki Sato;K. Nagai;N. Iizuka;M. Arito;Y. Takakuwa;H. Nakano;S. Ooka;N. Suematsu;K. Okamoto;K. Yudoh;Hiroshi Nakamura;N. Suzuki;S. Ozaki;Tomohiro Kato
T. Yoshioka;M. Kurokawa;Toshiyuki Sato;K. Nagai;N. Iizuka;M. Arito;Y. Takakuwa;H. Nakano;S. Ooka;N. Suematsu;K. Okamoto;K. Yudoh;Hiroshi Nakamura;N. Suzuki;S. Ozaki;Tomohiro Kato
中科院分区:
医学4区
文献类型:
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作者:
T. Yoshioka;M. Kurokawa;Toshiyuki Sato;K. Nagai;N. Iizuka;M. Arito;Y. Takakuwa;H. Nakano;S. Ooka;N. Suematsu;K. Okamoto;K. Yudoh;Hiroshi Nakamura;N. Suzuki;S. Ozaki;Tomohiro Kato

文献摘要

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为了研究白塞病(BD)的病理生理学并找到该疾病的生物标志物,我们分析了外周血单核细胞(PBMC)的蛋白质谱。方法采用二维差异凝胶电泳(2D-DIGE)对16例BD、16例类风湿关节炎(RA)、12例克罗恩病(CD)和16例健康对照者(HC)的PBMCs蛋白质进行综合分析。通过质谱法鉴定表达的蛋白质。结果共检测到563个蛋白点。我们完全区分BD和HC组之间,BD和RA组之间,BD和CD组之间的强度分别为23,35和1点的多变量分析。导致差异的点包括与细胞骨架、转录/翻译、T细胞活化、骨转换、调节细胞凋亡和微生物感染相关的蛋白质。3个点(酪氨酸蛋白磷酸酶非受体4型、苏氨酸磷酸酶样2和β-肌动蛋白)的强度提供了0.889的受试者工作特征曲线(AUROC)下面积,用于区分BD组和非BD组。信息上,上述1个斑点的强度完全区分CD组与其他组(AUROC 1.000)。这一点被鉴定为β-actin,其pI与上述β-actin点不同,可能是由于不同的翻译后修饰。结论PBMC蛋白质谱,尤其是3个斑点的蛋白质谱,可作为BD的候选生物标志物。后一种β-肌动蛋白亚型可用于区分炎症性肠病与BD和其他疾病。所鉴定的蛋白质可能在BD的病理生理学中起重要作用。
OBJECTIVES To investigate the pathophysiology of Behçet's disease (BD) and find biomarkers for the disease, we analysed protein profiles of peripheral blood mononuclear cells (PBMCs). METHODS Proteins, extracted from PBMCs, were comprehensively analysed in 16 patients with BD, 16 patients with rheumatoid arthritis (RA), 12 patients with Crohn's disease (CD), and 16 healthy control subjects (HC) by 2-dimensional differential gel electrophoResis (2D-DIGE). Differently expressed proteins were identified by mass spectrometry. RESULTS 563 protein spots were detected. We completely discriminated between the BD and HC groups, between the BD and RA groups, and between the BD and CD groups by multivariate analysis of intensity of 23, 35, and 1 spots, respectively. The spots contributing to the differences included proteins related to cytoskeleton, transcription/translation, T cell activation, bone turnover, regulating apoptosis, and microbial infection. Intensity of 3 spots (tyrosine-protein phosphatase non-receptor type 4, threonine synthase-like 2, and β-actin) provided area under the receiver operating characteristic curves (AUROC) of 0.889 for discrimination between the BD group and the non-BD groups. Informatively, intensity of the above 1 spot completely discriminated the CD group from the other groups (AUROC 1.000). This spot, identified as β-actin, had different pI from the above β-actin-spot probably due to different post-translational modification. CONCLUSIONS PBMC protein profiles, especially the profile of the 3 spots, would be candidate biomarkers for BD. The latter β-actin subtype would be useful for discriminating inflammatory bowel diseases from BD and other diseases. The identified proteins may play important roles in the pathophysiology of BD.