Towards an SI-Traceable Reference Measurement System for Seven Serum Apolipoproteins Using Bottom-Up Quantitative...

Area of Science:

• Clinical Chemistry
• Mass Spectrometry
• Cardiovascular Disease Research

Background:

• Current dyslipidemia management relies on traditional serum lipids, which inadequately capture lipid metabolism complexity in atherosclerotic cardiovascular disease (ASCVD) patients.
• Residual cardiovascular risk highlights limitations of current lipid panels, necessitating improved diagnostic approaches.
• Serum apolipoproteins (apos) like A-I, (a), B, C-I, C-II, C-III, and E offer enhanced pathophysiological insight into dyslipidemia.

Purpose of the Study:

• To outline a conceptual approach for developing a multiplexed Reference Measurement System (RMS) for seven key apolipoproteins.
• To facilitate the adoption of clinical serum apolipoprotein profiling for precision medicine in cardiovascular disease (CVD).
• To enable standardization of existing and emerging apolipoprotein assays to the International System of Units (SI).

Main Methods:

• Utilizing isotope dilution mass spectrometry (IDMS) for precise apolipoprotein quantification.
• Employing peptide-based calibration for accurate measurement.
• Leveraging advancements in mass spectrometry technology for reproducible protein quantification at the molecular level.
• Adhering to metrological traceability standards outlined in ISO 17511:2020.

Main Results:

• A novel, multiplexed Reference Measurement System (RMS) is proposed for seven apolipoproteins.
• The RMS aims to achieve standardization of apolipoprotein assays traceable to SI units.
• The system is designed for robustness and reproducibility, crucial for clinical application.

Conclusions:

• Standardization of apolipoprotein measurements is essential for advancing precision medicine in CVD.
• A robust RMS based on IDMS and peptide calibration can provide SI-traceable results.
• This approach addresses the unmet clinical need for comprehensive lipid metabolism assessment in dyslipidemia.