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Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-01-02 , DOI: 10.1093/infdis/jiz460
Anna Lena Jung 1 , Malene Møller Jørgensen 2 , Rikke Bæk 2 , Kathrin Griss 1, 3 , Maria Han 1, 4 , Kristina Auf Dem Brinke 1 , Nina Timmesfeld 5 , Wilhelm Bertrams 1 , Timm Greulich 6 , Rembert Koczulla 6 , Stefan Hippenstiel 3 , Norbert Suttorp 3 , Bernd Schmeck 1, 6, 7
Affiliation  

BACKGROUND Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) represent a major burden of disease and death and their differential diagnosis is critical. A potential source of relevant accessible biomarkers are blood-borne small extracellular vesicles (sEVs). METHODS We performed an extracellular vesicle array to find proteins on plasma sEVs that are differentially expressed and possibly allow the differential diagnosis between CAP and AECOPD. Plasma samples were analyzed from 21 healthy controls, 24 patients with CAP, and 10 with AECOPD . The array contained 40 antibodies to capture sEVs, which were then visualized with a cocktail of biotin-conjugated CD9, CD63, and CD81 antibodies. RESULTS We detected significant differences in the protein decoration of sEVs between healthy controls and patients with CAP or AECOPD. We found CD45 and CD28 to be the best discrimination markers between CAP and AECOPD in receiver operating characteristic analyses, with an area under the curve >0.92. Additional ensemble feature selection revealed the possibility to distinguish between CAP and AECOPD even if the patient with CAP had COPD, with a panel of CD45, CD28, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), tumor necrosis factor-R-II, and CD16. CONCLUSION The discrimination of sEV-associated proteins is a minimally invasive method with potential to discriminate between CAP and AECOPD.

中文翻译:

血浆细胞外囊泡的表面蛋白质组作为肺炎和慢性阻塞性肺疾病急性加重的生物标志物。

背景技术社区获得性肺炎(CAP)和慢性阻塞性肺疾病的急性加重(AECOPD)是疾病和死亡的主要负担,其鉴别诊断至关重要。相关的可利用生物标记物的潜在来源是血源性小细胞外囊泡(sEVs)。方法我们进行了细胞外囊泡阵列检测,以发现血浆sEVs上的蛋白表达差异,并可能对CAP和AECOPD进行鉴别诊断。分析了21名健康对照,24例CAP患者和10例AECOPD患者的血浆样品。该阵列包含40种捕获sEV的抗体,然后用生物素偶联的CD9,CD63和CD81抗体混合物进行可视化。结果我们发现健康对照与CAP或AECOPD患者之间sEV的蛋白修饰有显着差异。在接收器工作特性分析中,我们发现CD45和CD28是CAP和AECOPD之间的最佳区分标记,曲线下面积> 0.92。进一步的整体特征选择揭示了即使CAP患者患有COPD,也可以区分CAP和AECOPD,包括一组CD45,CD28,CTLA4(细胞毒性T淋巴细胞相关蛋白4),肿瘤坏死因子-R-II,和CD16。结论sEV相关蛋白的鉴别是一种微创方法,可以区分CAP和AECOPD。在接收器工作特性分析中,我们发现CD45和CD28是CAP和AECOPD之间的最佳区分标记,曲线下面积> 0.92。进一步的整体特征选择揭示了即使CAP患者患有COPD,也可以区分CAP和AECOPD,包括一组CD45,CD28,CTLA4(细胞毒性T淋巴细胞相关蛋白4),肿瘤坏死因子-R-II,和CD16。结论sEV相关蛋白的鉴别是一种微创方法,可以区分CAP和AECOPD。在接收器工作特性分析中,我们发现CD45和CD28是CAP和AECOPD之间的最佳区分标记,曲线下面积> 0.92。进一步的整体特征选择揭示了即使CAP患者患有COPD,也可以区分CAP和AECOPD,包括一组CD45,CD28,CTLA4(细胞毒性T淋巴细胞相关蛋白4),肿瘤坏死因子-R-II,和CD16。结论sEV相关蛋白的鉴别是一种微创方法,可以区分CAP和AECOPD。肿瘤坏死因子-R-II和CD16。结论sEV相关蛋白的鉴别是一种微创方法,可以区分CAP和AECOPD。肿瘤坏死因子-R-II和CD16。结论sEV相关蛋白的鉴别是一种微创方法,可以区分CAP和AECOPD。
更新日期:2019-12-30
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