Quantifying acute-phase inflammation proteins by NMR
The analysis of all small
molecules in an organism (the metabolome) has huge potential for medical diagnostics. A
German research team is investigating this with nuclear magnetic
resonance spectrometry (NMR). In a study recently published in Angewandte
Chemie, they quantified acute-phase proteins from serum samples that
act as markers for inflammatory diseases. They successfully obtained
several diagnostic parameters from a single, short, NMR experiment.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
In addition to genomics and proteomics, metabolomics is
becoming established as another mainstay of medical research and
diagnosis. Bodily fluids like blood are highly complex mixtures of only
partially known compounds. Metabolomic analysis is thus correspondingly
difficult and complex. A team led by Ulrich L. Günther and Alvaro
Mallagaray uses advanced NMR techniques to link the metabolomes of cells
and organisms to diseases.
NMR spectroscopy (NMR = nuclear magnetic resonance) is
based on the behavior – which varies depending on the chemical
environment – of magnetically active atomic nuclei, primarily hydrogen (1H)
and carbon (13C) under the influence of a strong external
magnetic field. Using this phenomenon, it is possible to obtain
measurements and characteristic spectra. In medical diagnosis, this
principle is also used in the form of MRI (magnetic resonance imaging)
to image tissue.
In prior studies, NMR measurements of blood serum produced
signals for special carbohydrate building blocks (acetyl resonances of N-acetylated
carbohydrates) that are linked to acute-phase glycoproteins. These
carbohydrate-containing proteins arise in cases of strong immune
responses to acute inflammation. As well as changes in their
concentration, their glycosylation pattern -- meaning the type, number,
and arrangement of their carbohydrate building blocks – can vary in a
specific way depending on the disease in question.
The team employed a series of different NMR processes to
fully assign the NMR signals from human serum. This led them to the
conclusion that the two strongest signals, designated as glycoproteins A
and B, result from N-acetylneuraminic acid and N-acetylglucosamine
building blocks, respectively, which contradicts a hypothesis proposed
in a prior study. By using diffusion-edited NMR experiments, they were
able to prove that the components of these signals can be tied to
specific, acute-phase proteins.
“NMR spectra allow for the simultaneous quantification of
several acute-phase inflammation proteins,” according to Ulrich L.
Günther. “A proteo-metabolomic NMR signature of significant diagnostic
potential is obtained within 10-20 minutes.” Working at the Universities
of Lübeck and Oldenburg, the University Hospitals of Greifswald and
Lübeck, the University Heart Center in Lübeck, and the German Center for
Cardiogenic Vascular Research (Greifswald and Lübeck), the team was able
to use serum samples from patients with COVID-19 or cardiogenic shock, a
dangerous side effect of heart attacks. In comparison to samples from
healthy individuals, they found significant changes in various specific
acute-phase proteins in the serum. In
the case of Parkinson’s disease, our method provides a yes-no diagnosis,
as Parkinson’s patients have a very specific glycosylation in their
blood that does not occur in healthy people,” Günther adds.
(3414 characters)
About the Author
Dr Ulrich Günther is a Professor at the University of
Lübeck and Director of the Institute of Chemistry and Metabolomics. He
has spent 15 years in the UK, where he directed the national NMR
facility at the University of Birmingham. Dr. Alvaro Mallagaray is a
senior scientist at the University of Lübeck. His main specialty is
Nuclear Magnetic Resonance and glycobiology, and the role of
glycosylation in health and disease. He is a Fellow of the Spanish Royal
Society of Chemistry and of the Spanish Society of Therapeutic
Chemistry, and is recipient of the Price for Excellence in Glycoscience
from the University of Hamburg.
Copy free of charge—we would appreciate a transcript/link of your
article. The original articles that our press releases are based on can
be found in our online pressroom.