Abstract
Proton nuclear magnetic resonance (NMR) N-acetyl signals (Glyc) from glycoproteins and supramolecular phospholipids composite peak (SPC) from phospholipid quaternary nitrogen methyls in subcompartments of lipoprotein particles) can give important systemic metabolic information, but their absolute quantification is compromised by overlap with interfering resonances from lipoprotein lipids themselves. We present a J-Edited DIffusional (JEDI) proton NMR spectroscopic approach to selectively augment signals from the inflammatory marker peaks Glyc and SPCs in blood serum NMR spectra, which enables direct integration of peaks associated with molecules found in specific compartments. We explore a range of pulse sequences that allow editing based on peak J-modulation, translational diffusion, and T2 relaxation time and validate them for untreated blood serum samples from SARS-CoV-2 infected patients (n = 116) as well as samples from healthy controls and pregnant women with physiological inflammation and hyperlipidemia (n = 631). The data show that JEDI is an improved approach to selectively investigate inflammatory signals in serum and may have widespread diagnostic applicability to disease states associated with systemic inflammation.
Highlights
Nuclear magnetic resonance (NMR) spectroscopy has been widely applied to multiple biomedical and physiological problems over the last three decades.[1]
Numerous inflammatory markers have been reported over the years including cytokines/chemokines,[19,20] lymphocytes,[21] C-reactive protein,[22] and prostaglandins,[23] there is an ongoing search for new inflammatory biomarkers and methodological approaches to quantify them quickly and more accurately
We demonstrate the J-Edited DIffusion (JEDI) NMR approach to recover metabolic inflammatory biomarker information using a mixed sample set from (1) patients infected with SARS-CoV-2 and their controls and (2) pregnant women
Summary
Nuclear magnetic resonance (NMR) spectroscopy has been widely applied to multiple biomedical and physiological problems over the last three decades.[1]. Bell et al first reported the application of proton NMR to detect α-1-acid-glycoprotein, an acute phase-reactive protein[13] in blood plasma associated with a number of inflammatory conditions. Acetyls of N-acetylglucosamino and N-acetyl-galactosamino groups in the oligosaccharide side chains of glycoproteins have been measured in multiple studies on inflammatory processes including cardiovascular diseases,[14] rheumatoid arthritis,[15] and chronic obstructive pulmonary disease.[16] Inflammation is a normal physiological protective response to common infections and tissue injury that can become excessive and harmful on its own when unregulated, for example in the socalled cytokine storm.[17] Inflammation is a mechanistically important part of most major diseases including cardiovascular disease, diabetes, cancers, and neurological conditions.[18] numerous inflammatory markers have been reported over the years including cytokines/chemokines,[19,20] lymphocytes,[21] C-reactive protein,[22] and prostaglandins,[23] there is an ongoing search for new inflammatory biomarkers and methodological approaches to quantify them quickly and more accurately
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