Marjot Jack, Liebetrau Christoph, Goodson Robert J, Kaier Thomas, Weber Ekkehard, Heseltine Peter, Marber Michael S
King's College London BHF Centre, The Rayne Institute, St Thomas' Hospital, London, UK.
Kerckhoff Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site RheinMain, Bad Nauheim, Germany.
Transl Res. 2016 Apr;170:17-25.e5. doi: 10.1016/j.trsl.2015.11.008. Epub 2015 Dec 8.
Cardiac troponins (cTns) are released and cleared slowly after myocardial injury. Cardiac myosin-binding protein C (cMyC) is a similar cardiac-restricted protein that has more rapid release and clearance kinetics. Direct comparisons are hampered by the lack of an assay for cMyC that matches the sensitivity of the contemporary assays for cTnI and cTnT. Using a novel pair of monoclonal antibodies, we generated a sensitive assay for MyC on the Erenna platform (Singulex) and compared serum concentrations with those of cTnI (Abbott) and cTnT (Roche) in stable ambulatory cardiac patients without evidence of acute cardiac injury or significant coronary artery stenoses. The assay for cMyC had a lower limit of detection of 0.4 ng/L, a lower limit of quantification (LLoQ) of 1.2 ng/L (LLoQ at 20% coefficient of variation [CV]) and reasonable recovery (107.1 ± 3.7%; mean ± standard deviation), dilutional linearity (101.0 ± 7.7%), and intraseries precision (CV, 11 ± 3%) and interseries precision (CV, 13 ± 3%). In 360 stable patients, cMyC was quantifiable in 359 patients and compared with cTnT and cTnI measured using contemporary high-sensitivity assays. cMyC concentration (median, 12.2 ng/L; interquartile range [IQR], 7.9-21.2 ng/L) was linearly correlated with those for cTnT (median, <3.0 ng/L; IQR, <3.0-4.9 ng/L; R = 0.56, P < 0.01) and cTnI (median, 2.10 ng/L; IQR, 1.3-4.2 ng/L; R = 0.77, P < 0.01) and showed similar dependencies on age, renal function, and left ventricular function. We have developed a high-sensitivity assay for cMyC. Concentrations of cMyC in clinically stable patients are highly correlated with those of cTnT and cTnI. This high correlation may enable ratiometric comparisons between biomarkers to distinguish clinical instability.
心肌损伤后，心肌肌钙蛋白（cTn）释放缓慢且清除也慢。心肌肌球蛋白结合蛋白C（cMyC）是一种类似的心脏特异性蛋白，其释放和清除动力学更快。由于缺乏一种与当代cTnI和cTnT检测方法灵敏度相匹配的cMyC检测方法，因此难以进行直接比较。我们使用一对新型单克隆抗体，在Erenna平台（Singulex）上开发了一种针对MyC的灵敏检测方法，并在无急性心脏损伤或明显冠状动脉狭窄证据的稳定门诊心脏病患者中，将血清浓度与cTnI（雅培）和cTnT（罗氏）的血清浓度进行了比较。cMyC检测方法的检测下限为0.4 ng/L，定量下限（LLoQ）为1.2 ng/L（20%变异系数[CV]时的LLoQ），回收率合理（107.1±3.7%；均值±标准差），稀释线性良好（101.0±7.7%），批内精密度（CV，11±3%）和批间精密度（CV，13±3%）。在360例稳定患者中，359例患者的cMyC可检测，将其与使用当代高灵敏度检测方法测得的cTnT和cTnI进行比较。cMyC浓度（中位数，12.2 ng/L；四分位数间距[IQR]，7.9 - 21.2 ng/L）与cTnT（中位数，<3.0 ng/L；IQR，<3.0 - 4.9 ng/L；R = 0.56，P < 0.01）和cTnI（中位数，2.10 ng/L；IQR，1.3 - 4.2 ng/L；R = 0.77，P < 0.01）呈线性相关，并且在年龄、肾功能和左心室功能方面表现出相似的相关性。我们开发了一种针对cMyC的高灵敏度检测方法。临床稳定患者中cMyC的浓度与cTnT和cTnI的浓度高度相关。这种高度相关性可能使生物标志物之间的比例比较能够区分临床不稳定性。
