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Towards a Precise NMR Quantification of Acute Phase Inflammation Proteins from Human Serum |
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| Authors: | Dr Alvaro Mallagaray Lorena Rudolph Melissa Lindloge Jarne Mölbitz Henrik Thomsen Dr Franziska Schmelter Mohamad Ward Alhabash Dr Mohammed R Abdullah Dr Roza Saraei Prof?Dr Marc Ehlers Dr Tobias Graf Prof?Dr Christian Sina Prof?Dr Astrid Petersmann Prof?Dr Matthias Nauck Prof?Dr Ulrich L Günther |
| Institution: | 1. Institute of Chemistry and Metabolomics, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany;2. Institute of Nutritional Medicine, University of Lübeck and Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany;3. Institute of Clinical Chemistry and Laboratory Medicine, Greifswald University Hospital, Fleischmannstraße 8, 17475 Greifswald, Germany;4. Department of Cardiology, Angiology and Intensive Care Medicine, University Heart Center Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
German Centre for Cardiogenic Vascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany;5. Institute of Nutritional Medicine, University of Lübeck and Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany Fraunhofer Research Institution for Individualized and Cell-Based Medical Engineering (IMTE), Mönkhofer Weg 239 a, 23538 Lübeck, Germany;6. Institute of Clinical Chemistry and Laboratory Medicine, Greifswald University Hospital, Fleischmannstraße 8, 17475 Greifswald, Germany Institute of Clinical Chemistry and Laboratory Medicine, Carl von Ossietzky University, Ammerländer Heerstraße 114–118, 26129 Oldenburg, Germany |
| Abstract: | Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N-glycans, respectively. Diffusion-edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins. Conventionally determined concentrations of acute phase glycoproteins correlate well with distinct features in NMR spectra (R2 up to 0.9422, p-value <0.001), allowing the simultaneous quantification of several acute phase inflammation proteins. Overall, a proteo-metabolomics NMR signature of significant diagnostic potential is obtained within 10–20 min acquisition time. This is exemplified in serum samples from COVID-19 and cardiogenic shock patients showing significant changes in several acute phase proteins compared to healthy controls. |
| Keywords: | Acute Phase Proteins Diagnostic Tool GlycA/B Glycoproteins NMR NMR Blood Analyses NMR Metabolomics |