摘要：背景：对常规DMARD无效的RA 患者可使用抗TNF治疗，抗TNF治疗的有效率为27%-56%，最近的研究显示，原癌基因生存素可预示关节破坏进展及不能获得临床缓解，且不依赖其他预后因素如抗CCP抗体或炎性水平。 目的 检测英夫利昔治疗是否可影响生存素水平及生存素是否可预测对英夫利昔的临床疗效。方法 来自Sahlgrenska大学医学院风湿病中心常规行英夫利昔输注的87例确诊RA患者(年龄24-89岁,女性占79%，病程18-526个月)。用ELISA测定生存素水平，测定65名健康人(年龄18-67岁)生存素水平作为正常值，低于0.9 ng/ml为阴性，高于该值 (0.9-3.9 ng/ml) 为阳性，高于4.0 ng/ml为高水平阳性。所有剂量的英夫利昔均检测生存素水平，采血时计算DAS28，计算在英夫利昔治疗期间的DAS28变化，DAS28≥1.2定义为有疗效。结果: 生存素的阳性率为36.8%（32/87），高水平生存素患者的比例随英夫利昔总量增高而逐步降低，英夫利昔累积量4000-8000 mg时最低(2/24, 8%)，英夫利昔治疗前基线DAS28值低的患者无1例有高水平生存素。高水平生存素患者的比例与DAS28成反比，在缓解组是最低的(DAS28<2 .6, 2/27, 7%)，如果das28高于3.2则明显增高 (10/39, 25.6%, p="0.002)。另外，与英夫利昔无反应组相比，反应组(DAS28下降≥" 1.2) 有高水平生存素的比例明显低(7/18 vs 5/45, p="0.01)。结论" :长期应用英夫利昔治疗期间的生存素水平降低，高水平的生存素常见于对英夫利昔无反应的ra患者。

附原文：Background: Anti-TNF treatment is an option of choice for the patients with RA resistant to conventional DMARDs. Response rate to anti-TNF treatment vary between 27-56%. We have recently shown that proto-oncogene survivin may serve as a predictor of progressive joint destruction and inability to achieve clinical remission. Its predictive value is independend on other prognostic factors as the presence of antiCCP-antibodies or level of inflammation.Objectives: The object of this study was to examine if infliximab treatment affects levels of survivin and if survivin may be used as a predictor of clinical response to infliximab.Methods: The study included 87 consecutive patients (age 24-89 years, females 79%) with established RA (disease duration 18-526 months) visiting Rheumatology Clinic, Sahlgrenska University Hospital for regular infusions of infliximab. Levels of survivin were assessed by an ELISA. The levels of survivin in 65 healthy controls (age 18-67 years) were used for estimation of cut-off levels. The levels below 0.9 ng/ml (mean+2SD of 65 healthy controls) were considered negative, the levels above were graded as positive (0.9-3.9 ng/ml) and high (above 4.0 ng/ml). Survivin levels were evaluated in relation to the total dose of infliximab, DAS28 at the time of blood sampling and the changes of DAS28 during infliximab treatment. Infliximab responders were defined as changes in DAS28≥1.2.Results: Positive levels of survivin were identified in 32/87 patients (36.8%). The proportion of patients having high levels of survivin decreased gradually with the accumulation of infliximab dose being lowest in patients with cumulative dose of infliximab between 4000-8000 mg (2/24, 8%). None of the patients with low DAS28 at baseline of infliximab treament had high survivin levels. The proportion of patients with high levels of survivin was inversly related to DAS28 at sampling being lowest in the remission group (DAS28<2 .6, 2/27, 7%) and increase significantly if das28 was above 3.2 (10/39, 25.6%, p="0.002)." additionally, high survivin was less frequent in clinical responders to infliximab (das28 decrease ≥ 1,2) as compared to non-responders (7/18 vs 5/45, p="0.01)." conclusion: our results indicate that survivin levels decrease during the long-term infliximab treatment and that high levels of survivin are frequently found in ra patients with poor response to infliximab treatment.

摘自：M Bokarewa, A Isgren, P Strzyz, et al. survivin levels is a marker of clinical response to infliximab treatment in patients with RA. Ann Rheum Dis 2010;69(Suppl3):199