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

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 (H-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 H-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 H-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 H-NMR launches an encouraging new paradigm for its future incorporation in clinical diagnosis.