Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany.
Clin Chem. 2021 Mar 1;67(3):478-489. doi: 10.1093/clinchem/hvaa239.
Current dyslipidemia management in patients with atherosclerotic cardiovascular disease (ASCVD) is based on traditional serum lipids. Yet, there is some indication from basic research that serum apolipoproteins A-I, (a), B, C-I, C-II, C-III, and E may give better pathophysiological insight into the root causes of dyslipidemia. To facilitate the future adoption of clinical serum apolipoprotein (apo) profiling for precision medicine, strategies for accurate testing should be developed in advance. Recent discoveries in basic science and translational medicine set the stage for the IFCC Working Group on Apolipoproteins by Mass Spectrometry. Main drivers were the convergence of unmet clinical needs in cardiovascular disease (CVD) patients with enabling technology and metrology. First, the residual cardiovascular risk after accounting for established risk factors demonstrates that the current lipid panel is too limited to capture the full complexity of lipid metabolism in patients. Second, there is a need for accurate test results in highly polymorphic and atherogenic apolipoproteins such as apo(a). Third, sufficient robustness of mass spectrometry technology allows reproducible protein quantification at the molecular level. Fourth, several calibration hierarchies in the revised ISO 17511:2020 guideline facilitate metrological traceability of test results, the highest achievable standard being traceability to SI. This article outlines the conceptual approach aimed at achieving a novel, multiplexed Reference Measurement System (RMS) for seven apolipoproteins based on isotope dilution mass spectrometry and peptide-based calibration. This RMS should enable standardization of existing and emerging apolipoprotein assays to SI, within allowable limits of measurement uncertainty, through a sustainable network of Reference Laboratories.
目前，动脉粥样硬化性心血管疾病（ASCVD）患者的血脂异常管理基于传统血清脂质。然而，一些基础研究表明，血清载脂蛋白 A-I、（a）、B、C-I、C-II、C-III 和 E 可能更好地洞察血脂异常的根本原因。为了促进未来临床血清载脂蛋白（apo）谱分析在精准医学中的应用，应提前制定准确检测的策略。基础科学和转化医学的最新发现为 IFCC 载脂蛋白质谱工作组奠定了基础。主要驱动力是心血管疾病（CVD）患者中未满足的临床需求与现有技术和计量学的融合。首先，在考虑到既定风险因素后，残留的心血管风险表明，目前的脂质谱过于有限，无法捕捉患者脂质代谢的全部复杂性。其次，需要对高度多态性和动脉粥样硬化载脂蛋白（如 apo(a)）进行准确的测试结果。第三，质谱技术具有足够的稳健性，允许在分子水平上进行可重复的蛋白质定量。第四，修订后的 ISO 17511:2020 指南中的几个校准层次有助于测试结果的计量溯源性，可实现的最高标准是与 SI 的溯源性。本文概述了旨在实现一种基于同位素稀释质谱和基于肽的校准的新型、多重参考测量系统（RMS）的概念方法，用于七种载脂蛋白。该 RMS 应通过参考实验室的可持续网络，在允许的测量不确定度范围内，使现有的和新兴的载脂蛋白检测标准化到 SI。
