Blackmore Sheena, Hamilton Malcolm, Lee Anne, Worwood Mark, Brierley Matthew, Heath Alan, Thorpe Susan J
UK NEQAS Scheme for Haematinics, Heart of England Foundation Trust, Good Hope Hospital, Sutton Coldfield, West Midlands, UK.
Clin Chem Lab Med. 2008;46(10):1450-7. doi: 10.1515/CCLM.2008.304.
Ferritin standardisation is problematical due to the heterogeneity of ferritin isoforms and the antibodies used in its immunoassay, and the lack of a reference measurement procedure. We investigated the performance of the 1st (liver), 2nd (spleen) and 3rd (recombinant) International Standards (ISs) for ferritin in major assays.
The ferritin in a serum pool 'spiked' with either the 2nd or 3rd IS for ferritin was measured by 52 laboratories using five automated methods and the recovery of the target values calculated. A smaller serum pool was 'spiked' with the 1st IS for a limited recovery exercise. The ferritin values of five serum samples were also measured and recalculated relative to the ISs.
Recoveries of each of the 2nd and 3rd ISs were 90%-110% for four of five methods; recoveries of the 1st IS were 104% and 111% for two of three methods claiming traceability to this IS. One method significantly over-recovered each of the IS (124%-155%). Recalculating the ferritin values of the serum samples relative to the IS reduced the overall inter-method agreement, largely because of the anomalous over-recovery of the IS by one method.
The use of the 3rd IS to standardise assays will minimise assay drift due to manufacturers adopting a 'harmonisation' approach in which the calibration is adjusted to conform to overall mean values. Standardisation against the current IS also ensures compliance with the European Union In-Vitro Diagnostic Directive which requires traceability of assay calibrators to reference materials of a higher order. Assay drift may result in poor sensitivity and specificity in the diagnosis of iron status, and would require laboratories to continually re-evaluate reference intervals.
由于铁蛋白异构体的异质性、免疫测定中使用的抗体以及缺乏参考测量程序，铁蛋白标准化存在问题。我们研究了铁蛋白第一（肝脏）、第二（脾脏）和第三（重组）国际标准品（ISs）在主要检测方法中的性能。
52个实验室使用五种自动化方法对添加了铁蛋白第二或第三国际标准品的血清混合液中的铁蛋白进行检测，并计算目标值的回收率。用较小的血清混合液添加铁蛋白第一国际标准品进行有限的回收率实验。还对五个血清样本的铁蛋白值进行了测量，并相对于国际标准品重新计算。
五种方法中的四种对第二和第三国际标准品的回收率均为90%-110%；三种声称可溯源至该国际标准品的方法中，有两种对第一国际标准品的回收率分别为104%和111%。有一种方法对每种国际标准品的回收率均显著过高（124%-155%）。相对于国际标准品重新计算血清样本的铁蛋白值降低了整体方法间的一致性，这主要是因为有一种方法对国际标准品的异常过高回收率。
使用第三国际标准品对检测进行标准化将使由于制造商采用“协调”方法（即调整校准以符合总体平均值）导致的检测漂移最小化。根据当前国际标准品进行标准化还可确保符合欧盟体外诊断指令，该指令要求检测校准品可溯源至更高等级的参考物质。检测漂移可能导致铁状态诊断的敏感性和特异性较差，并且需要实验室不断重新评估参考区间。
