类风湿关节炎并发间质性肺疾病患者血清蛋白质指纹图谱的临床价值分析

Clinical value analysis of serum protein fingerprint in patients with rheumatoid arthritis associated interstitial lung disease

目的:应用表面加强激光解吸电离飞行时间质谱筛选出类风湿关节炎并发间质性肺疾病(RA-ILD)患者血清中的差异蛋白,并对其临床价值进行初步分析。方法:用WCX2(弱阳离子交换芯片)蛋白芯片结合表面增强激光解吸电离飞行时间质谱(Surface enhanced laser desorption/ionization time of flight mass spectrum,SELDI-TOF-MS)检测19例RA-ILD患者,15例单纯RA、未合并间质性肺疾病患者,13例相对健康的对照组患者的血清样本,应用Biomarker Wizard软件、Biomarker Pattern软件以及SPSS13.0对测得的数据进行处理,初步构建分类树模型并随机选取部分病例进行验证。结果:患者血清中共检测出142个蛋白峰,经方差分析,发现了4个蛋白质峰差异有统计学意义,质荷比分别为3382.59、3453.39、11886.0、5825.48,Biomarker Pattern软件对所检测的所有数据分析后,发现以质荷比11689.4、2266.49、1020.22、4392.28、5074.38、2764.69为最适合建立分类树模型,灵敏度为92.31%(12/13),特异度为91.18%(31/34)。随机选取RA-ILD、RA、相对健康的对照组患者的血清样本各10例进行模型验证,灵敏度为90%(9/10),特异度为90%(18/20)。结论:SELDI-TOF-MS技术可筛选出RA-ILD患者血清中差异性表达蛋白,作为生物标志物,其诊断敏感度高,特异度好,对其测定具有较好的临床应用前景。

Objective： To screen differentially expressed proteins in serum proteomic patterns in patients with Rheumatoid Arthritis associated Interstitial Lung Disease by Surface enhanced laser desorption/ionization mass spectrometry with Protein Chip, and evaluate the value of a prelimina~ study. Methods： WCX2 （ Weak cation exchange chip） and Surface enhanced laser desorption/ ionization mass spectrometry with ProteinChip were performed to test serum proteins in 19 Rheumatoid Arthritis associated Interstitial Lung Disease, 15 Rheumatoid Arthritis patienfs and 13 health adults, Biomarker Wizard , Biomarker Pattern and Spssl3.0 software were used in combination to analyze the data. Results： The mass/charge ratio （M/Z） value of 142 protein peaks were detected in serum, there were 4 proteins differentially expressed with statistical significance among them （P〈0. 05; Student＇s t-test）, which were the proteins with M/Z 3382. 59,3453.39,11886. 0,5825.48 ; the proteins with M/Z 11689： 4,2266. 49,1020. 22,4392. 28,5074. 38 and 2764. 69 were selected to establish the optimal diagnostic model. The sensitivity was of was 90% （9/10）, the specificity was of 90% （18/20）. Conclusion： Surface enhanced laser desorption/ionization time of flight mass spectrum can screen out the significantly different proteins in serum of patients with Rheumatoid Arthritis associated Interstitial Lung Disease. As bomarkers, both of their sensitivity and specificity were high and determination have good prospects for clinical application.