研究作为哮喘潜在生物标志物的呼出气蛋白的新方法
2011/03/24
背景:哮喘是一种复杂的临床疾病,以气道炎症为主要特征。近期,诸多试验对呼出气冷凝液(EBC)进行了研究,旨在寻找哮喘的潜在生物标志物。然而,像哮喘这样一个复杂的疾病,一个生物标志物可能不足以用于早期诊断或随访。
目的:采用蛋白组学分析,研究疾病特异性蛋白水解肽或蛋白,寻找新的检测哮喘的蛋白。
方法:液相色谱和质谱用于分离和检测来自30名健康儿童和40名哮喘患儿(6~12 岁)的EBC中的蛋白(蛋白裂解肽)。
结果:支持向量机分析显示,不同哮喘状态存在不同的蛋白。这些蛋白裂解肽与一些已知的(如:肺活量、呼出气一氧化氮)及最近研究的呼出气标志物(EBC的pH值、LTB4)无明显相关。EBC中含量最多的是细胞角蛋白、白蛋白、肌动蛋白、血红蛋白、溶菌酶、皮离蛋白、钙粒蛋白B。
结论:虽然,本研究找到的一些蛋白裂解肽在疾病发展或气道生理状态下的具体作用尚不清楚,但寻找哮喘患者呼出气生物标志物是研究哮喘的很重要的一步。本研究找到的EBC中的蛋白,有可能成为后期哮喘无创性诊断或随访的一个感兴趣的指标。
(刘国梁 审校)
Clin Exp Allergy. 2010 Nov 24. doi: 10.1111/j.1365-2222.2010.03638.x. [Epub ahead of print]
A new approach to study exhaled proteins as potential biomarkers for asthma.
Bloemen K, Van Den Heuvel R, Govarts E, Hooyberghs J, Nelen V, Witters E, Desager K, Schoeters G.
Abstract
Background Asthma is a complex clinical disease characterized by airway inflammation. Recently, various studies reported on the analysis of exhaled breath condensate (EBC) in the search for potential biomarkers for asthma. However, in a complex disease such as asthma, one biomarker might not be enough for early diagnosis or follow-up. Objective The use of proteome analysis may reveal disease-specific proteolytic peptide or protein patterns, and may lead to the identification of novel proteins for the detection of asthma. Methods Liquid chromatography and mass spectrometry were used to separate and detect proteins (proteolytic peptides) present in EBC samples from 30 healthy children and 40 children with asthma in the age group of 6-12 years. Results Support vector machine analysis resulted in differentiating profiles based on asthma status. These proteolytic peptide patterns were not correlated to some well known (spirometry, exhaled nitric oxide) and more recently described exhaled markers (EBC pH, LTB(4) ). The more abundant proteins in EBC were identified as cytokeratins, albumin, actin, haemoglobin, lysozyme, dermcidin, and calgranulin B. Conclusion Although the exact role in the disease development or physiological state of the airways of the proteins described in the presented pattern is not clear at this moment, this is an important step in the search for exhaled biomarkers for asthma. This study shows that EBC contains proteins that are of interest for future non-invasive asthma diagnosis or follow-up.
Clin Exp Allergy. 2010 Nov 24. doi: 10.1111/j.1365-2222.2010.03638.x. [Epub ahead of print]
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严重哮喘生物学预测因素的种族差异:来自严重哮喘研究项目的数据
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吸入皮质激素治疗的哮喘患者呼出气一氧化氮与哮喘负担的关系