Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Proteomics Clin Appl. 2008 Jan;2(1):46-54. doi: 10.1002/prca.200780065. Epub 2007 Dec 17.
Asthma is the most common chronic disorder in childhood and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Allergic responses are known to be biased toward T-helper type 2 in asthmatics; however, the pathogenesis of asthma is not simple, and our understanding of the disease mechanism remains incomplete. The aim of the present study was to identify protein expression signatures that reflect acute exacerbation of asthma. Plasma was taken twice from pediatric asthmatic patients, once during asthma exacerbation and once during a stable period. Plasma was also taken from healthy children as a control. The protein profiles of plasma during asthma exacerbation were analyzed by 2-DE and 49 spots were differentially expressed during asthma exacerbation. Thirty-eight of the spots were successfully identified by MALDI-TOF MS. Proteins up- or down-regulated during asthma exacerbation were involved in responses to stress and pathogens, in the complement and coagulation cascades, and in acute-phase responses. Among the differentially expressed proteins, up-regulation of alpha-1-antitrypsin and complement component C7 was confirmed by nephelometry and ELISA. Our present results suggest that protease inhibitors and complement components may be involved in asthma exacerbation, and plasma level of alpha-1-antitrypsin may be a potential biomarker for asthma.
哮喘是儿童最常见的慢性疾病，哮喘恶化是儿童发病率和住院率的重要原因。已知哮喘患者的过敏反应偏向于辅助性 T 细胞 2 型；然而，哮喘的发病机制并不简单，我们对疾病机制的理解仍然不完整。本研究旨在确定反映哮喘急性恶化的蛋白质表达特征。从儿科哮喘患者身上抽取两次血浆，一次在哮喘恶化期间，一次在稳定期间。还从健康儿童身上抽取了血浆作为对照。通过 2-DE 分析哮喘恶化期间的血浆蛋白谱，在哮喘恶化期间有 49 个斑点差异表达。通过 MALDI-TOF MS 成功鉴定了 38 个斑点。哮喘恶化期间上调或下调的蛋白质参与了对压力和病原体的反应、补体和凝血级联反应以及急性期反应。在差异表达的蛋白质中，通过散射比浊法和 ELISA 证实了α-1-抗胰蛋白酶和补体成分 C7 的上调。我们目前的结果表明，蛋白酶抑制剂和补体成分可能参与哮喘恶化，α-1-抗胰蛋白酶的血浆水平可能是哮喘的潜在生物标志物。
