Development of a new immunoassay for the accurate determination of anti-infliximab antibodies in inflammatory bowel disease
Development of a new immunoassay for the accurate determination of anti-infliximab antibodies in inflammatory bowel disease
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DOI：
10.1007/s00535-011-0474-y
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发表时间：
2012-02-01
影响因子：
6.3
通讯作者：
Fujiyama, Yoshihide
中科院分区：
文献类型：
--
作者：
Imaeda, Hirotsugu;Andoh, Akira;Fujiyama, Yoshihide
英夫利西单抗（ATI）抗体的形成与炎症性肠病（IBD）患者对英夫利西单抗的应答丧失密切相关。我们评估了一种新的方法来测量血清ATI水平的英夫利西单抗存在的临床效用。ATI水平测定使用一种新的免疫测定法和传统的方法在58例克罗恩病（CD）患者在英夫利西单抗维持治疗。用酶联免疫吸附试验测定血清英夫利西单抗谷浓度，结果发现新方法检出ATI 16例（27.6%），而常规方法仅检出2例（3.4%）ATI滴度最高的患者。通过Western blot分析证实了新方法阳性但常规方法阴性的样品中存在ATI。Western印迹分析也表明，新方法可以恢复ATI的结合能力，其识别位点被游离英夫利西单抗占据。在新方法中，向样品中加入英夫利西单抗剂量依赖性地阻断了ATI的检测。与ATI阴性患者相比，ATI阳性患者的血清英夫利西单抗谷浓度显著降低（P <0.01），临床活动评分显著升高（P <0.001），新方法使在英夫利西单抗存在下测定血清ATI浓度成为可能。该方法可用于确定对英夫利西单抗无效的IBD患者的最佳治疗策略。
The formation of antibodies to infliximab (ATIs) is closely associated with the loss of response to infliximab in patients with inflammatory bowel disease (IBD). We evaluated the clinical utility of a novel method to measure serum ATI levels in the presence of infliximab.ATI levels were measured using a novel immunoassay and the conventional method in 58 patients with Crohn's disease (CD) under infliximab maintenance therapy. The serum infliximab trough levels were determined by enzyme-linked immunosorbent assay.ATIs were detected in 16 out of 58 patients (27.6%) by the new method, but the conventional method detected only 2 patients (3.4%) who had the two highest ATI titers assayed by the new method. The presence of ATIs in the samples positive by the new method but negative by the conventional method was confirmed by Western blot analysis. Western blotting analysis also indicated that the new method could restore the binding capacities of the ATIs whose recognition sites were occupied by free infliximab. In the new method, the addition of infliximab to the samples dose-dependently blocked the detection of ATIs. Patients positive for ATIs had significantly lower serum trough levels of infliximab (P < 0.01) and significantly higher clinical activity scores (P < 0.001) as compared with patients negative for ATI.The new method makes it possible to measure serum ATI levels in the presence of infliximab. This method is useful for deciding the optimal management strategies for IBD patients with loss of response to infliximab.