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  • GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation.

GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation.

Clinical chemistry (2015-03-18)
James D Otvos, Irina Shalaurova, Justyna Wolak-Dinsmore, Margery A Connelly, Rachel H Mackey, James H Stein, Russell P Tracy
ABSTRACT

Nuclear magnetic resonance (NMR) spectra of serum obtained under quantitative conditions for lipoprotein particle analyses contain additional signals that could potentially serve as useful clinical biomarkers. One of these signals that we named GlycA originates from a subset of glycan N-acetylglucosamine residues on enzymatically glycosylated acute-phase proteins. We hypothesized that the amplitude of the GlycA signal might provide a unique and convenient measure of systemic inflammation. We developed a spectral deconvolution algorithm to quantify GlycA signal amplitudes from automated NMR LipoProfile(®) test spectra and assessed analytic precision and biological variability. Spectra of acute-phase glycoproteins and serum fractions were analyzed to probe the origins of the GlycA signal. GlycA concentrations obtained from archived NMR LipoProfile spectra of baseline plasma from 5537 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were used to assess associations with demographic and laboratory parameters including measures of inflammation. Major acute-phase protein contributors to the serum GlycA signal are α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA concentrations were correlated with high-sensitivity C-reactive protein (hsCRP) (r = 0.56), fibrinogen (r = 0.46), and interleukin-6 (IL-6) (r = 0.35) (all P < 0.0001). Analytic imprecision was low (intra- and interassay CVs 1.9% and 2.6%, respectively) and intraindividual variability, assessed weekly for 5 weeks in 23 healthy volunteers, was 4.3%, lower than for hsCRP (29.2%), cholesterol (5.7%), and triglycerides (18.0%). GlycA is a unique inflammatory biomarker with analytic and clinical attributes that may complement or provide advantages over existing clinical markers of systemic inflammation.

MATERIALS
Product Number
Brand
Product Description

SAFC
Cholesterol, Plant-Derived, SyntheChol®
Sigma-Aldrich
Cholesterol, from lanolin, ≥99.0% (GC)
Sigma-Aldrich
SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, aqueous solution, sterile-filtered, suitable for cell culture
Sigma-Aldrich
N-Acetyl-D-glucosamine, ≥95% (HPLC)
Sigma-Aldrich
Sodium bromide, BioUltra, ≥99.0% (AT)
Sigma-Aldrich
Sodium bromide, ≥99.99% trace metals basis
Sigma-Aldrich
Sodium bromide, BioXtra, ≥99.0%
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
Cholesterol, from sheep wool, ≥92.5% (GC), powder
Sigma-Aldrich
Cholesterol, Sigma Grade, ≥99%
Sigma-Aldrich
N-Acetyl-D-glucosamine, ≥99% (HPLC)
Sigma-Aldrich
N-Acetyl-D-glucosamine, BioReagent, suitable for cell culture
SAFC
Cholesterol, from sheep wool, Controlled origin, meets USP/NF testing specifications
Sigma-Aldrich
Sodium bromide, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99%