目的:用纳米磁珠与基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)技术检测原发性干燥综合征(primary Sjgren’s syndrome,pSS)合并肺间质病变(interstitial lung disease,ILD)患者血清蛋白质组,筛选候选蛋白标志物并建立诊断模型,初步探讨所建立的诊断模型在pSS-ILD诊断中的临床意义。方法:采用弱阳离子(WCX)纳米磁性微球捕获69例pSS患者血清中的蛋白质,所获蛋白质经PBSⅡ-C蛋白质芯片阅读仪绘制蛋白指纹图谱,经Ciphergen ProteinChip和Biomarker Wizard软件分析之后,再用Biomarker Patterns软件识别,最终筛选出pSS-ILD的特异性蛋白标志物,并优化组合建立诊断模型。结果:在pSS-ILD患者和对照组之间共找到7个差异蛋白峰(P〈0.05),其中质荷比(m/z)为3 778.3、3 318.3和2 236.6的3个蛋白峰用于建立pSS-ILD诊断模型,该模型对pSS-ILD诊断的敏感性为93.1%,特异性为87.5%。经双盲实验验证,该模型对pSS-ILD诊断的敏感性为84%,特异性为85.7%。结论:应用WCX纳米磁性微球联合MALDI-TOF-MS技术可检出pSS-ILD患者血清中的特异性蛋白标志物,并建立敏感性和特异性均较好的pSS-ILD诊断模型。
Objective:To detect the serum protein biomarkers and establish a diagnostic model for primary Sjgren's syndrome(pSS) with interstitial lung disease(ILD).Methods: Serum samples from 69 patients with pSS were prepared with WCX magnetic beads,and analyzed on PBSⅡ-C mass spectrometer reader.Biomarker Wizard software was used to detect protein peaks and potential difference between the patients with pSS-ILD and with non-ILD.The model was developed by Biomarker Patterns software.Results: Totally 7 discriminative mass-to-charge(m/z) ratios were identified to be related with pSS-ILD(P0.05).Among these,the m/z peaks at 3 778.3,3 318.3 and 2 236.6 were used to construct a diagnostic model.The sensitivity and specificity of the model were 93.1% and 87.5%,respectively.In a testing set,the sensitivity and specificity of the model were 84.0% and 85.7%,respectively.Conclusion: The potential protein biomarkers for pSS-ILD are discovered in the serum by MALDI-TOF-MS combined with WCX magnetic beads.The diagnostic pattern combining 3 778.3,3 318.3 and 2 236.6 m/z protein peaks can discriminate pSS-ILD and non-ILD.