Towards a Precise NMR Quantification of Acute Phase Inflammation Proteins from Human Serum

Alvaro Mallagaray*, Lorena Rudolph, Melissa Lindloge, Jarne Mölbitz, Henrik Thomsen, Franziska Schmelter, Mohamad Ward Alhabash, Mohammed R. Abdullah, Roza Saraei, Marc Ehlers, Tobias Graf, Christian Sina, Astrid Petersmann, Matthias Nauck, Ulrich L. Günther*

*Corresponding author for this work

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 languageEnglish
Article numbere202306154
JournalAngewandte Chemie - International Edition
Volume62
Issue number35
Pages (from-to)e202306154
ISSN1433-7851
DOIs
Publication statusPublished - 28.08.2023

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Cardiological Center Luebeck (UHZL)

DFG Research Classification Scheme

  • 204-05 Immunology

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