Title: Human Serum/Plasma Glycoprotein Analysis by 1H-NMR, an Emerging Method of Inflammatory Assessment

Abstract

Several studies suggest that variations in the concentration of plasma glycoproteins can influence cellular changes in a large number of diseases. In recent years, proton nuclear magnetic resonance (1H-NMR) has played a major role as an analytical tool for serum and plasma samples. In recent years, there is an increasing interest in the characterization of glycoproteins through 1H-NMR in order to search for reliable and robust biomarkers of disease. The objective of this review was to examine the existing studies in the literature related to the study of glycoproteins from an analytical and clinical point of view. There are currently several techniques to characterize circulating glycoproteins in serum or plasma, but in this review, we focus on 1H-NMR due to its great robustness and recent interest in its translation to the clinical setting. In fact, there is already a marker in H-NMR representing the acetyl groups of the glycoproteins, GlycA, which has been increasingly studied in clinical studies. A broad search of the literature was performed showing a general consensus that GlycA is a robust marker of systemic inflammation. The results also suggested that GlycA better captures systemic inflammation even more than C-reactive protein (CRP), a widely used classical inflammatory marker. The applications reviewed here demonstrated that GlycA was potentially a key biomarker in a wide range of diseases such as cancer, metabolic diseases, cardiovascular risk, and chronic inflammatory diseases among others. The profiling of glycoproteins through 1H-NMR launches an encouraging new paradigm for its future incorporation in clinical diagnosis.

A Tale of Two Biomarkers: Untargeted 1H NMR Metabolomic Fingerprinting of BHBA and NEFA in Early Lactation Dairy Cows

“…Upfield regions of spectra were dominated by branched-chain amino acids (leucine, isoleucine and valine), organics acids (BHBA, lactate, acetate) and the methyl and methylene groups of low density (LDL) and very low density lipoproteins (VLDL) at δ 0.86 ppm and δ 1.25 ppm, respectively [32]. We also observed a prominent peak at δ 2.03 ppm which was consistent with the N-acetyl groups of glycoproteins [33]. The singlet at δ 3.14 ppm was identified as dimethyl sulfone (DMSO 2 ) [34,35].…”

“…In dairy cattle, increased serum NEFA concentrations in early lactation are associated with uncontrolled inflammation, and this inflammatory dysfunction is hypothesized to be a central link between metabolic and infectious disorders [14,47]. 1 H NMR spectroscopy is showing promise for the quantification of glycoprotein A (GlcA) in human research into metabolic diseases such obesity, diabetes mellitus and the metabolic syndrome [33]. Given that these syndromes have much in common with early lactation metabolic disease in dairy cows (e.g., insulin resistance), we believe that further research into GlcA as a biomarker for early lactation health is warranted.…”

Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection

“… 40 This has been subsequently demonstrated and explored by other groups 43 and is the subject of a recent comprehensive review. 44 Multiple inflammatory associations and correlations between Glyc A and blood triglycerides and lipids, branched chain amino acids and between Glyc A, and Glyc B and insulin resistance, prediction of future glycemia, associations of Glyc A with higher IL-6 and C-reactive protein and future development of Type 2 Diabetes mellitus have been observed. 45 Elevation of the Glyc A signal has shown to be associated with cardiovascular disease and with severity in several inflammatory diseases.…”

GlycA Levels during the Earliest Stages of Rheumatoid Arthritis: Potential Use as a Biomarker of Subclinical Cardiovascular Disease

“…Although, in previous years, there was limited access to core facilities with H-NMR technology, this is becoming more available nowadays. Moreover, its longer stability and reliability may facilitate the logistic aspect behind their use as a biomarker (reviewed in [ 54 ]). Of note, GlycA testing may have important advantages over the use of ultrasound imaging techniques, as it can be automated and processed in batch, in a less time-consuming and operator bias-free way.…”

“…Of note, GlycA testing may have important advantages over the use of ultrasound imaging techniques, as it can be automated and processed in batch, in a less time-consuming and operator bias-free way. Finally, the fact that NMR measurement allows a simultaneous lipoprotein characterization provides additional advantages, in relation to cost-effectiveness as well [ 6 , 54 ].…”