Towards an SI-traceable Reference Measurement System for seven Serum Apolipoproteins using bottom-up Quantitative Proteomics: Conceptual Approach enabled by Cross-Disciplinary/Cross-Sector Collaboration

Current dyslipidemia management in patients with atherosclerotic cardiovascular disease (ASCVD) is based on traditional serum lipids. Yet, strong indications from basic research indicate that serum apolipoproteins A-I, (a), B, C-I, C-II, C-III and E give better pathophysiological insight in the root causes of dyslipidemia. To ensure the coming-of-age and future clinical adoption of serum apolipoprotein (apo) profiling for precision medicine, the path to accurate testing should pro-actively be prepared. Recent discoveries triggered the establishment of an IFCC Working Group on Apolipoproteins by Mass Spectrometry. Main drivers were the convergence of unmet clinical needs in cardiovascular disease (CVD) patients, and enabling technology and metrology. First, the unsolved residual cardiovascular risk in high risk patients demonstrates that the current serum lipid panel is too limited to capture the full CVD complexity in patients. Second, there is a need for accurate, unconfounded test results in highly polymorphic and atherogenic apolipoproteins such as apo(a). Third, sufficient robustness of mass spectrometry technology allows reproducible protein quantitation at the molecular level. Fourth, the perspective of several calibration hierarchies in the revised ISO 17511:2020 guideline facilitates metrological traceability of test results, the highest achievable being traceability to SI. Here the authors outline their conceptual approach towards a novel, multiplexed Reference Measurement System (RMS) for seven apolipoproteins based on isotope dilution mass spectrometry and peptide-based calibration. In the nearby future, this RMS should enable standardization of contemporary and emerging apo tests to SI, within allowable limits of measurement uncertainty, through a sustainable network of Reference Laboratories.

COBBAERT C.M.;  ALTHAUS Harald;  BEGCEVIC I.;  CEGLAREK U.;  COASSIN Stefan;  DELATOUR Vincent;  DEPREZ Liesbet;  DIKAIOS Ioannis;  DITTRICH L.;  HOOFNAGLE A.;  KOSTNER G.M.;  KRONENBERG F.;  KUKLENYIK Z;  PRINZING U.;  VESPER Hubert;  ZEGERS Ingrid;  RUHAAK L. R.; 

2021-07-07

OXFORD UNIV PRESS INC

JRC121356

0009-9147 (online),   

https://academic.oup.com/clinchem/article/67/3/478/6040690,    https://publications.jrc.ec.europa.eu/repository/handle/JRC121356,   

10.1093/clinchem/hvaa239 (online),