蛋白指纹图谱技术筛选神经精神狼疮的生物标志物  

Surrogate biomarkers identification for neuropsychiatric lupus by proteomic fingerprint technology

作　　者：陈焕[1] 孙玲[1] 陈华[1] 胡朝军[1] 李永哲[1] 王彭[2] 谢静[2] 巴德年[3] 何维[3] 张烜[1] 

机构地区：[1]中国医学科学院北京协和医院风湿免疫科,100730 [2]中国医学科学院北京协和医院中心实验室,100730 [3]中国协和医科大学基础医学院免疫学教研室

出　　处：《中华风湿病学杂志》2012年第6期402-405,共4页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（30400410,30972731）;国家重点基础研究发展计划（973计划子课题）（2007CB,512405）;教育部新世纪优秀人才计划（NCET-04-0191）;北京自然科学基金（7052052）

摘　　要：目的通过基质辅助激光解吸电离飞行时间质谱（MALDI．TOF—MS）联合弱阳离子交换（WCX）磁珠法分析神经精神狼疮（NPSLE）患者脑脊液蛋白质谱，建立树形分类模型并验证其诊断价值。方法MALDI—TOF—MS联合WCX磁珠法生成脑脊液蛋白质谱，比较NPSLE治疗前组（27例）与对照组（27例）蛋白质谱，采用t检验、Kmskal．WallisH检验和Wilcoxon检验分析2组间及NPSLE组治疗前后差异峰，建立NPSLE树形分类模型。以独立样本（12例NPSLE、12例腰椎间盘突出和9例其他自身免疫病的中枢神经系统受累患者）盲法检验该树形分类模型对诊断NPSLE的敏感性和特异性。结果NPSLE治疗前组与对照组、NPSLE治疗前组与治疗后组相比，分别有12个和4个差异峰。以质荷比（na／z）8595、7170、7661、7740和5806差异峰建立NPSLE树形分类模型，对54例建模组的敏感性和特异性均为92．6％，对33例独立样本盲法检验的敏感性和特异性分别为91．7％和85．7％。结论本研究首次建立了MALDI—TOF．MS联合WCX磁珠法检测NPSLE脑脊液蛋白质谱的方法，据此建立的NPSLE树形分类模型对诊断NPSLE具有较高的敏感性和特异性。Objective To identify biomarkers in cerebrospinal fluid （CSF） by proteomic technology and develop a diagnostic model for neuropsychiatric lupus （NPSLE）. Methods CSF proteomic spectra of 27 patients with NPSLE before and after treatment, and 27 controls including 17 patients with scoliosis, and 10 SLE patients without neuropsychiatric manifestation （non-NPSLE） were generated by matrix assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS） combined with weak cationic exch- ange （WCX） magnetic beads. Data were analyzed with t test, non-parametric Kruskal-Wallis H test or Wilco- xon sign-rank test. A decision tree model for NPSLE classification was built based on the discriminating peaks. In addition, CSF samples of 12 patients with NPSLE, 12 patients with lumbar disc herniation and 9 patients with other neurological conditions were employed as blind test group to verify the accuracy of the model. Results Twelve discriminating mass-to-charge （m/z） peaks were identified between NPSLE and controls. The diagnostic decision tree model, built with a panel of m/z peaks 8595, 7170, 7661, 7740 and 5806, recogn- ized NPSLE with the sensitivity and specificity of 92.6% and 92.6% based on training group samples, 91.7% and 85.7% based on blind test group,respectively. Conclusion Potential CSF NPSLE biomarkers are identified by proteomic technology, the novel diagnostic model is sensitive and relatively specific for the diagnosis of NPSLE.

关 键 词：狼疮血管炎 中枢神经系统 生物学标记 蛋白指纹图谱技术 

分 类 号：R593.241[医药卫生—内科学]