应用蛋白指纹图谱筛选肿瘤坏死因子抑制剂治疗类风湿关节炎的生物标志物  

Screening for Specific Biomarkers in Tumor Necrosis Factor Inhibitor Treated Rheumatoid Arthritis Patients using Proteomic Fingerprint Technology

作　　者：史群[1] 林玮[1] 胡朝军[1] 白伊娜[1] 张文[1] 张奉春[1] 

机构地区：[1]中国医学科学院 北京协和医学院 北京协和医院风湿免疫科,北京100032

出　　处：《中华临床免疫和变态反应杂志》2013年第1期16-21,共6页Chinese Journal of Allergy & Clinical Immunology

基　　金：国家自然科学基金面上项目(81172858)

摘　　要：目的通过蛋白组学研究发现与肿瘤坏死因子(tumor necrosis factor,TNF)单克隆抗体治疗类风湿关节炎(rheumatoid arthritis,RA)疗效相关的新的血清生物标志物。方法入组患者为17例经传统改善病情抗风湿药治疗后病情仍为中至重度活动性RA患者,分别在第0、2、6、14和22周联合英夫利西单抗(200mg/次)静脉滴注。分别留取治疗前(第0周)、治疗中(第14周)及治疗后(第26周)血清,并进行详细临床病情评估。使用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)方法检测血清中蛋白组学。结果英夫利西单抗治疗后临床改善者13例(76.5%),无改善者4例(23.5%)。在治疗有效的患者中,蛋白组学分析共有10种小分子蛋白水平随治疗而下降;而治疗无效的患者上述10种蛋白水平无显著变化。此外,无论是治疗有效还是治疗无改善的患者血清中均有2种蛋白分子峰值随治疗升高。结论利用蛋白组学方法可发现与TNF抑制剂治疗相关的血清蛋白标志物,这些标志物可能有助于预测TNF抑制剂的有效性。Objective To screen for the potential protein biomarkers in rheumatoid arthritis （RA） patients who received tumor necrosis factor （TNF） monoclonal antibody （infliximab） therapy by using proteomic fingerprint technology. Methods Seventeen RA patients with moderate to severe disease activity were enrolled in this study. All patients were given an intravenous infusion of 200 mg infliximab at Week O, 2, 6, 14 and 22, respectively. Clinical assessment was done at each visit. Serum samples were collected, and proteomic fingerprint technology combining magnetic beads with MALDI-TOFMS was used to analyze serum proteins. Results After infliximab treatment, 13 （76.5%） patients had clinical improvement, while 4 （23.5%） patients failed the treatment. Among those with clinical improvement, MALDI-TOFMS analysis showed 10 proteins decreased with infliximab treatment, while there was no change in those without improvement. Meanwhile, two kinds of proteins increased both in effective patients and non-effective patients.Conclusions Biomarkers for evaluation of efficacy of anti-TNF monoclonal discovered in serum by MALDI-TOF-MS combining the use of magnetic beads. markers provides possible predictors for efficacy of TNF inhibitor treatment. antibody therapy can be The pattern of combined

关 键 词：类风湿关节炎 肿瘤坏死因子抑制剂 蛋白组学 

分 类 号：R446.8[医药卫生—诊断学]