HDL particle number measured on the Vantera®, the first clinical NMR analyzer

Matyus, Steven P.; Braun, Paul; Wolak-Dinsmore, Justyna; Saenger, Amy K.; Jeyarajah, Elias J.; Shalaurova, Irina; Warner, Suzette M.; Fischer, Timothy J.; Connelly, Margery A.

doi:10.1016/j.clinbiochem.2014.11.017

Cited by 56 publications

(65 citation statements)

References 31 publications

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“…Analysis was performed using 6 replicates for each pool. The results of the spiked pools were compared to their corresponding controls by paired difference test [26]. When the difference in results was statistically significant, the difference was checked whether it was considered clinically significant.…”

Section: Methodsmentioning

confidence: 99%

“…While sensitive and rapid, they require use of a synthetic stable isotope labeled internal standard, uniquely trained personnel, and specialized and expensive equipment not always available in the clinical diagnostic laboratory. The addition of an automated, high-throughput nuclear magnetic resonance (NMR) analyzer to the clinical diagnostic lab has recently become a reality [25, 26]. Here, we present a simple, automated NMR spectroscopy-based assay for quantification of TMAO.…”

Section: Introductionmentioning

confidence: 99%

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NMR quantification of trimethylamine- N -oxide in human serum and plasma in the clinical laboratory setting

Garcia¹,

Wolak-Dinsmore²,

Wang

et al. 2017

Clinical Biochemistry

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Background and objectives Trimethylamine-N-oxide (TMAO) produced by gut microbiota metabolism of dietary choline and carnitine has been shown to be associated with increased risk of cardiovascular disease (CVD) and to provide incremental clinical prognostic utility beyond traditional risk factors for assessing a patient’s CVD risk. The aim of this study was to develop an automated nuclear magnetic resonance (NMR) spectroscopy assay for quantification of TMAO concentration in serum and plasma using a high-throughput NMR clinical analyzer. Methods Key steps in assay development included: (i) shifting the TMAO analyte peak to a less crowded region of the spectrum with a pH buffer/reagent, (ii) attenuating the broad protein background signal in the spectrum and (iii) using a non-negative least squares algorithm for peak deconvolution. Assay performance was evaluated according to Clinical and Laboratory Standards Institute guidelines. A method comparison study was performed to compare TMAO concentrations quantified by NMR and mass spectrometry (MS). Results The within-run and within-lab imprecision ranged from 4.3 to 14.5%. Under the acquisition method employed, the NMR assay had a limit of blank, detection and quantitation of 1.6, 3.0 and 3.3 μM, respectively. Linearity was demonstrated within the reportable range of 3.3 to 3,000 μM. TMAO measurements using the NMR assay, which involves minimal sample preparation, compared well with values obtained with the MS-based assay (R2 = 0.98). Conclusions The NMR based assay provides a simple and accurate measurement of circulating TMAO levels amenable to the high-throughput demands of the clinical chemistry laboratory. Moreover, assay performance enables the levels of TMAO to be quantified in serum or plasma at clinically actionable concentrations for the assessment of cardiovascular disease risks and individualized dietary monitoring.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NMR quantification of trimethylamine- N -oxide in human serum and plasma in the clinical laboratory setting

Garcia¹,

Wolak-Dinsmore²,

Wang

et al. 2017

Clinical Biochemistry

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“…An effort was made to choose patients and visits such that each patient has at least one visit with high disease activity and one visit with low disease activity. Sera were analyzed for lipoprotein particle and GlycA concentrations using NMR performed on the Vantera Clinical Analyzer using the methods outlined by Otvos et al and Matyus et al (19, 25, 26). Patients were evaluated longitudinally to determine how lipoprotein parameters change with time, treatment and other clinical variables.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Evaluation of Lipoprotein Variables in Systemic Lupus Erythematosus Reveals Adverse Changes with Disease Activity and Prednisone and More Favorable Profiles with Hydroxychloroquine Therapy

Durcan

Winegar²,

Connelly³

et al. 2016

J Rheumatol

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Objectives Systemic lupus erythematosus (SLE) associates with accelerated atherosclerotic cardiovascular disease. SLE patients have adverse lipoprotein parameters, but little is known about how these change with treatment and disease activity. The NMR LipoProfile test® contains a glycoprotein signal termed GlycA, an inflammatory marker, which has not been evaluated in SLE. We assessed patients longitudinally to determine how lipoproteins and GlycA change with active SLE. Methods Sera from selected clinical visits of patients in the Hopkins Lupus Cohort were analyzed for lipoprotein and GlycA levels. Univariate and multivariate analyses were performed to evaluate lipoprotein parameters and their relationship to ethnicity, disease activity, prednisone use and hydroxychloroquine therapy. Results 52 patients were included over 229 visits. Adverse changes in lipoprotein parameters with disease activity were demonstrated. For each point increase in SLEDAI there was a decrease in high-density lipoprotein (HDL) even after adjusting for corticosteroid use. Prednisone associated with higher VLDL, LDL, HDL and triglycerides. Hydroxychloroquine associated with more favorable parameters. GlycA levels were higher than in normal populations and increased with disease activity. Conclusion Adverse changes in lipoprotein profiles associated with SLE activity and prednisone therapy. This gives insight into mechanisms of atherosclerosis in SLE. Favorable lipoprotein parameters occurred in those taking hydroxychloroquine. GlycA increased with disease activity and was higher than in healthy populations.

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“…Proton ( 1 H) NMR, another high-throughput technological platform that is able to quantify inflammatory glycoproteins based on their glycans, was recently introduced to the clinical laboratory setting [38][39][40][41][42][43]. Although it is not possible to identify and quantify individual proteins via NMR, it is possible to measure subsets of glycoproteins based on their shared glycan moieties [38,39,42].…”

Section: Assays Of Glycoproteins In Biological Fluids and Developmentmentioning

confidence: 99%

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

Connelly

Gruppen

Otvos

et al. 2016

Clinica Chimica Acta

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The physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease states. In fact, glycan processing contributes to pathogenicity not only in autoimmune disorders but also in atherosclerotic cardiovascular disease, diabetes and malignancy. While most clinical laboratory tests measure circulating levels of inflammatory proteins, newly developed diagnostic and prognostic tests are harvesting the information that can be gleaned by measuring the amount or structure of the attached glycans, which may be unique to individuals as well as various diseases. As such, these newer glycan-based tests may provide future means for more personalized approaches to patient stratification and improved patient care. Here we will discuss recent progress in high-throughput laboratory methods for glycomics (i.e. the study of glycan structures) and glycoprotein quantification by methods such as mass spectrometry and nuclear magnetic resonance spectroscopy. We will also review the clinical utility of glycoprotein and glycan measurements in the prediction of common low-grade inflammatory disorders including cardiovascular disease, diabetes and cancer, as well as for monitoring autoimmune disease activity.

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HDL particle number measured on the Vantera®, the first clinical NMR analyzer

Abstract: The performance characteristics, as well as the primary tube sampling procedure for specimen analysis on the Vantera(®) Clinical Analyzer, suggest that the HDL-P assay is suitable for routine clinical applications.

Cited by 56 publications

References 31 publications

NMR quantification of trimethylamine- N -oxide in human serum and plasma in the clinical laboratory setting

NMR quantification of trimethylamine- N -oxide in human serum and plasma in the clinical laboratory setting

Longitudinal Evaluation of Lipoprotein Variables in Systemic Lupus Erythematosus Reveals Adverse Changes with Disease Activity and Prednisone and More Favorable Profiles with Hydroxychloroquine Therapy

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

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