title: GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  GlycA is a unique inflammatory biomarker with analytic and clinical attributes that may complement or provide advantages over existing clinical markers of systemic inflammation.
authors.affiliation: LabCorp, Raleigh, NC; otvosj@labcorp.com.
authors.forename: James D
authors.initials: JD
authors.lastname: Otvos
authors.affiliation: LabCorp, Raleigh, NC;
authors.forename: Irina
authors.initials: I
authors.lastname: Shalaurova
authors.affiliation: LabCorp, Raleigh, NC;
authors.forename: Justyna
authors.initials: J
authors.lastname: Wolak-Dinsmore
authors.affiliation: LabCorp, Raleigh, NC;
authors.forename: Margery A
authors.initials: MA
authors.lastname: Connelly
authors.affiliation: University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA;
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Mackey
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, WI;
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.affiliation: Department of Pathology, University of Vermont College of Medicine, Colchester, VT.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011134:Polysaccharides / Q000737:chemistry*; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology*
chemical_list: D011134:Polysaccharides; D000117:Acetylglucosamine