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.
| Original language | English |
|---|---|
| Article number | e202306154 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 62 |
| Issue number | 35 |
| Pages (from-to) | e202306154 |
| ISSN | 1433-7851 |
| DOIs | |
| Publication status | Published - 28.08.2023 |
Funding
C.S. thanks Fresenius Kabi GmbH for research funding. F.S. was supported by the Damp Foundation. We thank the Rotary Club Lübeck Burgtor and the VDI programme of the BMBF (grant no 13GW0592E, REMOLCO) for support of this project. We would like to thank Prof. Thomas Peters (University of Lübeck, Germany) for helpful advice. We also thank Dr. Mario Schubert (University of Salzburg, Austria) for fruitful discussions and Prof. Norbert Tautz and Dr. Olaf Isken (University of Lübeck, Germany) for granting us access to the facilities and equipment at the Institute of Virology. We also thank Prof Brian Schaffhausen (Tufts University) for critical proofreading and for various discussions at different stages of the manuscript. Open Access funding enabled and organized by Projekt DEAL. C.S. thanks Fresenius Kabi GmbH for research funding. F.S. was supported by the Damp Foundation. We thank the Rotary Club Lübeck Burgtor and the VDI programme of the BMBF (grant no 13GW0592E, REMOLCO) for support of this project. We would like to thank Prof. Thomas Peters (University of Lübeck, Germany) for helpful advice. We also thank Dr. Mario Schubert (University of Salzburg, Austria) for fruitful discussions and Prof. Norbert Tautz and Dr. Olaf Isken (University of Lübeck, Germany) for granting us access to the facilities and equipment at the Institute of Virology. We also thank Prof Brian Schaffhausen (Tufts University) for critical proofreading and for various discussions at different stages of the manuscript. Open Access funding enabled and organized by Projekt DEAL.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
- Centers: Cardiological Center Luebeck (UHZL)
DFG Research Classification Scheme
- 2.21-05 Immunology
