哮喘和慢性阻塞性肺疾病新的诊断性生物标志物
2011/06/17
摘要
原理：采用蛋白组学，发现了一些可用于鉴别哮喘和慢性阻塞性肺疾病(COPD)的生物标志物。
目的：对哮喘和COPD诊断明确的患者外周血蛋白进行无监督分析，寻找并证实鉴别两者的生物标志物。
方法：采用二维差异性凝胶电泳(2D-DIGE)分离健康对照者、稳定哮喘患者和COPD患者的血浆蛋白。采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)寻找候选蛋白标志物，通过免疫分析，在两类人群中进行证实。共找到4个生物标志物，这些标志物单独和联合用于鉴别哮喘和COPD的作用分别在2个验证人群中进行评价。
结果：72个蛋白位点在三组人群中存在差异性表达(p<0.05)。找到58个阳性蛋白，代表的是20个独特蛋白。一组4个生物标志物（a-2巨球蛋白、结合珠蛋白、铜蓝蛋白和血红素结合蛋白）能用于鉴别哮喘、COPD和对照，这些结果在患气流梗阻的年长成人中得到证实。
结论：蛋白组学研究找到了鉴别哮喘和COPD的新生物标志物，结果显示，铁代谢通路和急性期反应可能参与了气道疾病的致病过程。一些外周血生物标志物可作为呼吸道疾病诊断和治疗的有益辅助。
（刘国梁 审校）
Am J Respir Crit Care Med. 2011 Mar 18. [Epub ahead of print]
Identification of Novel Diagnostic Biomarkers for Asthma and Chronic Obstructive Pulmonary Disease.
Verrills NM, Irwin JA, He XY, Wood LG, Powell H, Simpson JL, McDonald VM, Sim A, Gibson PG.
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia; CRC for Asthma and Airways, Sydney, New South Wales, Australia.
Abstract
RATIONALE: Proteomics may identify a useful panel of biomarkers for identification of asthma and chronic obstructive pulmonary disease (COPD).
OBJECTIVES: To conduct an unsupervised analysis of peripheral blood proteins in well characterised subjects with asthma and COPD, and identify and validate a biomarker panel for disease discrimination.
METHODS: Two-dimensional difference gel electrophoresis (2D-DIGE) was used to separate plasma proteins from healthy controls, stable asthmatics and individuals with COPD. Candidate protein markers were identified using matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF MS) and subsequently validated in two populations via immunoassay. A panel of four biomarkers was selected and their ability to distinguish between groups assessed in isolation and in combination in 2 separate validation populations.
RESULTS: Seventy-two protein spots displayed significantly different expression levels between the three subject groupings (p<0.05). 58 were positively identified representing 20 unique proteins. A panel of four biomarkers (a-2 macroglobulin, haptoglobin, ceruloplasmin and hemopexin) was able to discriminate with statistical significance between the clinical groups of asthma, COPD, and controls, and these results were confirmed in a second clinical population of older adults with airflow obstruction.
CONCLUSIONS: Proteomics has identified novel biomarkers for asthma and COPD, and shown that the iron metabolism pathways and acute phase response may be involved in the pathogenesis of airway disease. The panel of peripheral blood biomarkers has the potential to become an extremely useful addition to the clinical diagnosis and management of respiratory disease.
Am J Respir Crit Care Med. 2011 Mar 18. [Epub ahead of print]
原理：采用蛋白组学，发现了一些可用于鉴别哮喘和慢性阻塞性肺疾病(COPD)的生物标志物。
目的：对哮喘和COPD诊断明确的患者外周血蛋白进行无监督分析，寻找并证实鉴别两者的生物标志物。
方法：采用二维差异性凝胶电泳(2D-DIGE)分离健康对照者、稳定哮喘患者和COPD患者的血浆蛋白。采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)寻找候选蛋白标志物，通过免疫分析，在两类人群中进行证实。共找到4个生物标志物，这些标志物单独和联合用于鉴别哮喘和COPD的作用分别在2个验证人群中进行评价。
结果：72个蛋白位点在三组人群中存在差异性表达(p<0.05)。找到58个阳性蛋白，代表的是20个独特蛋白。一组4个生物标志物（a-2巨球蛋白、结合珠蛋白、铜蓝蛋白和血红素结合蛋白）能用于鉴别哮喘、COPD和对照，这些结果在患气流梗阻的年长成人中得到证实。
结论：蛋白组学研究找到了鉴别哮喘和COPD的新生物标志物，结果显示，铁代谢通路和急性期反应可能参与了气道疾病的致病过程。一些外周血生物标志物可作为呼吸道疾病诊断和治疗的有益辅助。
（刘国梁 审校）
Am J Respir Crit Care Med. 2011 Mar 18. [Epub ahead of print]
Identification of Novel Diagnostic Biomarkers for Asthma and Chronic Obstructive Pulmonary Disease.
Verrills NM, Irwin JA, He XY, Wood LG, Powell H, Simpson JL, McDonald VM, Sim A, Gibson PG.
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia; CRC for Asthma and Airways, Sydney, New South Wales, Australia.
Abstract
RATIONALE: Proteomics may identify a useful panel of biomarkers for identification of asthma and chronic obstructive pulmonary disease (COPD).
OBJECTIVES: To conduct an unsupervised analysis of peripheral blood proteins in well characterised subjects with asthma and COPD, and identify and validate a biomarker panel for disease discrimination.
METHODS: Two-dimensional difference gel electrophoresis (2D-DIGE) was used to separate plasma proteins from healthy controls, stable asthmatics and individuals with COPD. Candidate protein markers were identified using matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF MS) and subsequently validated in two populations via immunoassay. A panel of four biomarkers was selected and their ability to distinguish between groups assessed in isolation and in combination in 2 separate validation populations.
RESULTS: Seventy-two protein spots displayed significantly different expression levels between the three subject groupings (p<0.05). 58 were positively identified representing 20 unique proteins. A panel of four biomarkers (a-2 macroglobulin, haptoglobin, ceruloplasmin and hemopexin) was able to discriminate with statistical significance between the clinical groups of asthma, COPD, and controls, and these results were confirmed in a second clinical population of older adults with airflow obstruction.
CONCLUSIONS: Proteomics has identified novel biomarkers for asthma and COPD, and shown that the iron metabolism pathways and acute phase response may be involved in the pathogenesis of airway disease. The panel of peripheral blood biomarkers has the potential to become an extremely useful addition to the clinical diagnosis and management of respiratory disease.
Am J Respir Crit Care Med. 2011 Mar 18. [Epub ahead of print]
上一篇：
诱导痰液中嗜酸性粒细胞的简化检测方法
下一篇：
难治性哮喘患者声带功能异常
