Sensitivity and specificity of detection methods for erythropoietin doping in cyclists
Sensitivity and specificity of detection methods for erythropoietin doping in cyclists
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DOI：
10.1002/dta.2665
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发表时间：
2019-07-17
影响因子：
2.9
通讯作者：
Cohen, Adam F.
中科院分区：
文献类型：
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作者：
Heuberger, Jules A. A. C.;van Eenoo, Peter;Cohen, Adam F.
重组人促红细胞生成素（rHuEPO）是用作兴奋剂的一种物质。反兴奋剂工作包括尿液和血液检测以及监测运动员生物护照（ABP）。由于这些方法的性能数据不完整，本研究旨在评价两种常见尿液检测试剂盒和ABP的性能。在一项随机、双盲、安慰剂对照试验中，48名受过训练的自行车运动员接受了平均剂量为6000 IU的rHuEPO（依泊苷β）或安慰剂，每周注射一次，持续8周。每例受试者采集7份定时尿液和血液样本。在根特经认证的DoCoLab中，通过肌氨酰-PAGE和等电聚焦方法分析尿样。选择的样品，包括任何错误的推定结果，进行了第二次肌氨酰-PAGE确认分析。血液学参数用于构建类似于ABP的模块，并由来自运动员护照管理单位的两名评估员进行分析。肌氨酰聚丙烯酰胺凝胶电泳和等电聚焦检测促红细胞生成素滥用的敏感性分别为63.8%和58.6%，假阳性率分别为4.3%和6%。在确认分析中，没有一个错误的推定结果是阳性的。给药后2 - 6天的灵敏度最高，在此时间窗外迅速下降。ABP的灵敏度为91.3%。尿液检测的特异性高，然而，rHuEPO的检测窗口是狭窄的，导致可疑的灵敏度。综合纵向数据的ABP更加敏感，但仍有一些主题逃避检测。结合这些方法可能会提高性能，但不会解决所有观察到的缺点。
Recombinant human erythropoietin (rHuEPO) is used as doping a substance. Anti-doping efforts include urine and blood testing and monitoring the athlete biological passport (ABP). As data on the performance of these methods are incomplete, this study aimed to evaluate the performance of two common urine assays and the ABP. In a randomized, double-blinded, placebo-controlled trial, 48 trained cyclists received a mean dose of 6000 IU rHuEPO (epoetin beta) or placebo by weekly injection for eight weeks. Seven timed urine and blood samples were collected per subject. Urine samples were analyzed by sarcosyl-PAGE and isoelectric focusing methods in the accredited DoCoLab in Ghent. A selection of samples, including any with false presumptive findings, underwent a second sarcosyl-PAGE confirmation analysis. Hematological parameters were used to construct a module similar to the ABP and analyzed by two evaluators from an Athlete Passport Management Unit. Sensitivity of the sarcosyl-PAGE and isoelectric focusing assays for the detection of erythropoietin abuse were 63.8% and 58.6%, respectively, with a false presumptive finding rate of 4.3% and 6%. None of the false presumptive findings tested positive in the confirmation analysis. Sensitivity was highest between 2 and 6 days after dosing, and dropped rapidly outside this window. Sensitivity of the ABP was 91.3%. Specificity of the urine assays was high; however, the detection window of rHuEPO was narrow, leading to questionable sensitivity. The ABP, integrating longitudinal data, is more sensitive, but there are still subjects that evade detection. Combining these methods might improve performance, but will not resolve all observed shortcomings.