Department of Biotechnology, University of Turku, Turku, Finland.
Clin Chem. 2012 Jun;58(6):1040-8. doi: 10.1373/clinchem.2011.179226. Epub 2012 Apr 9.
Autoantibodies to cardiac troponins (cTnAAb) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays. The aim of this study was to explore the degree of cTnAAb interference in different cTnI assay configurations.
Ternary troponin complex was added into samples (serum or plasma, n = 132, 68% cTnAAb positive) from individuals without known cardiac conditions. The recovery of cTnI was then measured with 6 investigational cTnI assays (2, 3, or 4 antibodies per assay). Three of these assays were then selected for further comparison by use of samples (plasma, n = 210, 33% cTnAAb positive) from non-ST-elevation acute coronary syndrome patients in the FRISC-II (FRagmin/Fast Revascularisation during InStability in Coronary artery disease) cohort. Finally, these results were compared to those obtained with 3 commercial cTnI assays.
Analytical recoveries varied widely among the 6 investigational assays. Notably the low recoveries (median 9%) of the midfragment-targeting reference assay were normalized (median 103%) with the use of the 4-antibody assay construct (3 capture, 1 tracer antibody) with only 1 antibody against a midfragment epitope. Reduced analytical recoveries correlated closely with measured autoantibody amounts. cTnI concentrations from cTnAAb-positive patient samples determined with 3 investigational assays confirmed the reduced concentrations expected from the low analytical recoveries. The results from the commercial cTnI assays with antibody selections representative for contemporary assay constructs revealed a similar underestimation (up to 20-fold) of cTnI in cTnAAb-positive samples.
A novel cTnI assay deviating from the conventional IFCC-recommended midfragment approach substantially improves cTnI detection in samples containing cTnAAbs.
心肌肌钙蛋白（cTn）自身抗体（cTnAAb）可干扰免疫分析法检测心肌肌钙蛋白 I（cTnI）。本研究旨在探讨不同 cTnI 检测方法中 cTnAAb 干扰的程度。
将三元肌钙蛋白复合物添加到来自无已知心脏疾病个体的血清或血浆样本中（n=132，68% cTnAAb 阳性）。然后用 6 种研究中的 cTnI 检测方法（每个检测方法 2、3 或 4 种抗体）测量 cTnI 的回收率。然后选择其中 3 种检测方法，使用 FRISC-II（不稳定型冠状动脉疾病中 Fragmin/快速血运重建）队列中的非 ST 段抬高型急性冠状动脉综合征患者的血浆样本（n=210，33% cTnAAb 阳性）进一步比较。最后，将这些结果与 3 种商业 cTnI 检测方法的结果进行比较。
6 种研究中的检测方法的分析回收率差异很大。值得注意的是，中片段靶向参考检测方法的低回收率（中位数 9%）通过使用仅有一种针对中片段表位的抗体的 4 种抗体检测结构（3 种捕获抗体，1 种示踪抗体）得到了校正（中位数 103%）。分析回收率降低与测定的自身抗体量密切相关。用 3 种研究中的检测方法测定的 cTnAAb 阳性患者样本中的 cTnI 浓度证实了预期的低分析回收率导致的浓度降低。具有代表性的当代检测结构的抗体选择的商业 cTnI 检测方法的结果显示，cTnAAb 阳性样本中 cTnI 的浓度也出现了类似的低估（高达 20 倍）。
一种偏离传统 IFCC 推荐的中片段方法的新型 cTnI 检测方法可显著提高含有 cTnAAb 的样本中 cTnI 的检测。
