应用蛋白质指纹技术筛选强直性脊柱炎血清特异性标志物的临床研究  

Protein fingerprinting for screening specific biomarkers in serum of patients with ankylosing spondylitis

作　　者：马丹[1] 张莉芸[1] 张改连[1] 许珂[1] 侯睿宏[1] 高晋芳[1] 

机构地区：[1]山西医学科学院山西大医院风湿免疫科,山西太原030032

出　　处：《中国实用内科杂志》2017年第3期233-237,共5页Chinese Journal of Practical Internal Medicine

基　　金：山西省卫生厅科技攻关项目(2011003)

摘　　要：目的应用表面增强激光解析离子化-飞行时间质谱技术(surface-enhanced laser desorption ioni zation/time of flight mass spectrometry,SELDI-TOF-MS)和蛋白质芯片筛选强直性脊柱炎(ankylosing spondylitis,AS)患者血清特异性标志物,用于疾病诊断、评估及预测病情进展。方法采用SELDI-TOF-MS技术和弱阳离子交换(weak cation exchange)芯片检测2008年4月至2009年1月山西医科大学第二医院风湿免疫科收治的69例AS患者及12名健康对照者、10例类风湿关节炎(rheumatoid arthritis,RA)患者血清蛋白质表达,进一步将AS患者分为活动期与非活动期,中轴关节受累及中轴、外周关节均受累,HLA-B27阳性与阴性组,比较不同分组之间患者血清蛋白质指纹图谱,采用SELDI质谱仪自带的Biomarker Wizard和Biomarker Pattern软件筛选,初步建立疾病诊断预测模型。结果由8085、2640和2932建立的诊断预测模型Ⅰ诊断AS的敏感度为94.23%,特异度为100%。由3677、3880、2539、3159和3242建立的诊断预测模型Ⅱ判断病情活动的敏感度为98.11%,特异度为100%。由4700、8687和18538建立的诊断预测模型Ⅲ预测AS同时有中轴及外周关节受累的敏感度为80.00%,特异度为82.35%。由10259、7972、2048、2154和2954建立的诊断模型Ⅳ区分AS和RA的敏感度为100%(69/69),特异度为100%(10/10)。结论通过SELDI-TOF-MS技术建立的血清蛋白质指纹图谱可以筛选AS患者血清中的特异性蛋白质标志物,有望成为诊断疾病及评估病情的一种初筛平台。Objective The surface-enhanced laser desorption ionization/time of flight mass spectrometry （SELDI-TOF-MS） and protein chip was used for screening specific biomarkers in serum of patients with ankylosing spondylitis （AS） to diagnose and assess the disease as well as to anticipate the progress of disease. Methods The serum samples of 69 AS patients, 10 patients with rheumatoid arthritis and 12 healthy individuals were detected by SELDI-TOF-MS and weak cation exchange chip. Then 69 AS patients were divided into several groups such as the active and inactive stage of illness, axial arthritis involved and peripheral and axial arthritis involved, and the positive and negative group of HLA-B27, to study proteins differentially expressed in the pathogenesis of AS. By using Biomarker Wizard and Biomarker Pattern software of SELDI to screen the specific proteins, set up the diagnostic prediction models of disease. Results The first diagnostic modeI made up of 8085, 2640 and 2932 could be used to diagnose AS, whose the sensitivity and specificity were 94.23% and 100% respectively. The second diagnostic model made up of 3677, 3880, 2539, 3159 and 3242 could be used to determine the disease activity of AS, whose the sensitivity and specificitywere 98.11% and 100% respectively： The third diagnostic model made up of 4700, 8687 and 18538 could be used to predict AS, whether peripheral arthritis be involved or not, whose the sensitivity and specificity were 80.00% and 82.35% respectively： The fourth diagnostic model made up of 10259, 7972, 2048, 2154 and 2954 could be used to distinguish AS from RA, whose the sensitivity and specificity were 100% and 100% respectively. Conclusion The serum protein fingerprinting set up by SELDI-TOF-MS can screen specific protein biomarkers in AS, which is expected to become a screening platform in diagnosis and assessment of disease.

关 键 词：脊柱炎 强直性 蛋白质指纹图谱 表面增强激光解析离子化-飞行时间质谱 蛋白质芯片 血清 

分 类 号：R593.23[医药卫生—内科学]