1H-NMR glycoprotein analysis: An Advanced approach for inflammatory diseases diagnosis

Identifier:  TDX:2978

Handle: https://hdl.handle.net/20.500.11797/TDX2978

Authors:  Fuertes Martín,Rocio

Abstract:
Inflammation is a complex biological response of an organism to a stimulus of diverse aetiology. During the inflammatory response there is a variation in the concentrations of certain proteins present in plasma called acute phase proteins. Most of these proteins are glycated proteins. The process of protein glycation increases in response to pro-inflammatory cytokines and is characterized by the binding of one or more monosaccharides (such as GlcNAc, GalNAC and Neu5Ac, among others) to the amino acid chain of the protein. Currently there is a growing interest in the discovery of new biomarkers capable of evaluating the degree of systemic inflammation due in part to the great intra-individual variability that present the markers currently used in clinical such as CRP. In recent years, high-performance NMR technology has become an increasingly used tool in clinical practice due to its great advantages. An example of this are the advanced lipoprotein tests (e.g. Liposcale in Biosfer Teslab or Lipoprofile in Labcorp). In this thesis we present a method of quantification of glycoproteins based on NMR in order to determine their clinical interest. Unlike other NMR methods described in the literature that quantify GlycA and GlycB, corresponding to the concentration of the acetyl groups of GlcNAc, GalNac and Neu5AC residues, we present new parameters not previously described such as GlycF and the H/W ratios of GlycA and GlycB, which have been shown to be strongly associated with the degree of inflammation. The results obtained in the studies presented in this thesis are promising from a clinical and methodological point of view. The profiling of glycoproteins through 1H-NMR, launches an encouraging new paradigm for its future incorporation in clinical diagnosis.