Serum Nuclear Magnetic Resonance Spectroscopy: One More Step toward Clinical Utility

Ala‐Korpela, Mika

doi:10.1373/clinchem.2015.238279

Cited by 25 publications

(23 citation statements)

References 17 publications

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“…We found that concentrations of the low-grade inflammatory markers CRP and GlycA were clearly increased during pregnancy, suggesting the up-regulation of systemic maternal inflammation. The new inflammatory marker, GlycA, which is quantified via the serum NMR metabolomics platform, has recently been shown to be associated with both acute-phase and chronic inflammation, as well as being related to increased neutrophil activities [27, 49]. Elevation of GlycA during pregnancy may thereby suggest an enhancement of maternal innate immunity.…”

Section: Discussionmentioning

confidence: 99%

Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence

Wang

Würtz

Auro

et al. 2016

BMC Med

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BackgroundPregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood.MethodsDetailed molecular profiles (87 metabolic measures and 37 cytokines) were measured for up to 4260 women (24–49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status.ResultsCompared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters.ConclusionsPregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0733-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence

Wang

Würtz

Auro

et al. 2016

BMC Med

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163

172

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“…GlycA is an NMR-based biomarker predictive of morbidity and mortality from diverse disease outcomes [3][4][5][6][7][8][9][10][11][12][13]19 . It is composed of the concentrations of multiple circulating glycoproteins [13][14][15] , each of which respond to myriad inflammatory stimuli 20 .…”

Section: Discussionmentioning

confidence: 99%

“…Of recent interest is the GlycA biomarker, a serum NMR signal that has been shown to be highly predictive of morbidity and mortality from diverse diseases 3,4 , including cardiovascular diseases [5][6][7][8] , certain cancers [7][8][9] , type II diabetes 5,10,11 , liver diseases 5,12 , chronic inflammatory conditions 5,8 , renal failure 5 , severe infections 13 , and all-cause mortality 7,8 . Elevated GlycA levels are associated with inflammation arising from recent infection, injury, or chronic disease [14][15][16][17][18] , as well as low-grade chronic inflammation that may persist for up to a decade in otherwise apparently healthy adults 13 .…”

Section: Introductionmentioning

confidence: 99%

“…Of recent intense interest is the GlycA biomarker, a serum NMR signal associated with acute and chronic inflammation that has been shown to be highly predictive of morbidity and mortality from diverse diseases, as well as being largely independent of C-reactive protein (CRP) [3][4][5][6][7][8][9][10][11][12][13][14] . The GlycA signal is an agglomeration of at least five circulating glycoprotein concentrations: predominantly alpha-1 antitrypsin (AAT), alpha-1-acid glycoprotein (AGP), haptoglobin (HP), transferrin (TF), and alpha-1-antichymotrypsin (AACT) 15,16 .…”

Section: Introductionmentioning

confidence: 99%

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Elevated alpha-1 antitrypsin is a major component of GlycA-associated risk for future morbidity and mortality

Ritchie

Kettunen

Brożyńska

et al. 2018

Preprint

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Integration of electronic health records with systems-level biomolecular data has led to the discovery that GlycA, a complex nuclear magnetic resonance (NMR) spectroscopy biomarker, predicts long-term risk of disease onset and death from myriad causes. To fine-map the molecular underpinnings of the disease risk of the heterogeneous GlycA signal, we used machine learning to build imputation models for GlycA's constituent glycoproteins, then estimated glycoprotein levels in 11,861 adults across two population-based cohorts with long-term follow-up. While alpha-1-acid glycoprotein had the strongest correlation with GlycA, our analysis revealed that alpha-1 antitrypsin (AAT) was the most predictive of morbidity and mortality for the widest range of diseases, including heart failure (HR=1.60 per s.d., P=1´10-10

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“…In proton ( 1 H) NMR spectra of blood plasma or serum, measured as part of clinical lipoprotein testing 5 or for NMR-based metabolomics research, 6 a prominent signal appears at 2.00±0.01 ppm arising from the mobile N-acetyl methyl protons of a subset of glycan N-acetylglucosamine residues (specifically those in β1→2 and β1→6 linkages with preceding mannose sugars). This signal been given the name GlycA 5 and is contributed to by many circulating glycoproteins, but for reasons of relative abundance reflects primarily the glycan on 5 major acute-phase inflammatory proteins and immune modulators: α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin.…”

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confidence: 99%