Targeted multiplex proteomics for prediction of all-cause mortality during long-term follow-up in outpatients with peripheral arterial disease

Skau, Emma; Henriksen, Egil; Leppert, Jerzy; Wagner, Philippe; Ärnlöv, Johan; Hedberg, Pär

doi:10.1016/j.atherosclerosis.2020.06.015

Cited by 6 publications

(5 citation statements)

References 36 publications

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“…The multiplex PEA is a relatively new high-throughput technique increasingly used in human biomarker research. Many promising prognostic biomarkers have been detected using the PEA technique [ 15 , 16 , 26 , 27 ]. However, the PEA data are expressed in relative NPX-unit whereas conventional immunoassays present absolute concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…A random individual with the closest date of birth, same sex, and same municipality as an included VaMIS patient was invited to participate. The patients from the PADVa cohort and controls in the VaMIS study underwent the same study protocol [ 15 ]. From the 855 control subjects in the VaMIS study, 175 individuals (20.5%) were excluded as they fulfilled the criteria for PAD specified above.…”

Section: Methodsmentioning

confidence: 99%

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Are the results from a multiplex proteomic assay and a conventional immunoassay for NT-proBNP and GDF-15 comparable?

et al. 2023

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Background We aimed to compare absolute plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) obtained by a conventional immunoassay with the corresponding relative concentrations from a proximity extension assay (PEA) and compare the prognostic impact of the protein levels obtained from these assays. Methods We evaluated 437 patients with peripheral arterial disease (PAD) and a population-based cohort of 643 individuals without PAD. Correlations were calculated using Spearman’s rank correlation coefficients (rho). The discriminatory accuracy of the protein levels to predict future cardiovascular events was analyzed with Cox regression and presented as time-dependent areas under the receiver-operator-characteristic curves (tdAUCs). Results For NT-proBNP, the two assays correlated with rho 0.93 and 0.93 in the respective cohort. The PEA values leveled off at higher values in both cohorts. The corresponding correlations for GDF-15 were 0.91 and 0.89. At 5 years follow-up, the tdAUCs in the patient cohort were similar for NT-proBNP and GDF-15 regardless of assay used (0.65–0.66). The corresponding tdAUCs in the population-based cohort were between 0.72 and 0.77. Conclusion Except for the highest levels of NT-proBNP, we suggest that PEA data for NT-proBNP and GDF-15 reliably reflects absolute plasma levels and contains similar prognostic information.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Are the results from a multiplex proteomic assay and a conventional immunoassay for NT-proBNP and GDF-15 comparable?

et al. 2023

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“…[ 59 ] Other studies have confirmed that GDF-15 may be an effective predictor of all-cause mortality in LEAD patients. [ 60 , 61 ] Thus, circulating GDF-15 could be of value in predicting which CLTI patients would benefit from intensified treatment and/or surgical intervention.…”

Section: Circulating Biomarkersmentioning

confidence: 99%

Circulating Biomarkers in Lower Extremity Artery Disease

2022

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Lower extremity artery disease (LEAD), a chronic condition with disturbed lower extremity circulation due to narrowing of the arteries, is predominantly caused by atherosclerosis and is associated with the presence of cardiovascular risk factors and an increased risk of cardiovascular events. LEAD is prevalent among older individuals and predicted to rise with the ageing population. In progressive disease, the patient experiences symptoms of ischaemia when walking and, in advanced critical limb-threatening ischaemia, even at rest. However, LEAD is asymptomatic in most patients, delaying diagnosis and treatment. In this setting, circulating biomarkers may facilitate earlier diagnosis in selected individuals. This review provides a broad overview of the circulating biomarkers investigated to date in relation to LEAD and discusses their usefulness in clinical practice.

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“…PEA was first described by Lundberg et al in 2011 [ 1 ], for the detection of protein biomarkers in liquid samples. Several improvements were subsequently made with a focus on the potential of the technique for multiplex assays, as applied to the fields of proteomics and biomarker screening [ 4 – 6 ]. For each biomarker, a pair of antibodies conjugated to unique oligonucleotides (henceforth referred to as PEA probes or PEA conjugates) binds to their respective epitope.…”

Section: Introductionmentioning

confidence: 99%

Procalcitonin detection in human plasma specimens using a fast version of proximity extension assay

et al. 2023

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An exciting trend in clinical diagnostics is the development of easy-to-use, minimally invasive assays for screening and prevention of disease at the point of care. Proximity Extension Assay (PEA), an homogeneous, dual-recognition immunoassay, has proven to be sensitive, specific and convenient for detection or quantitation of one or multiple analytes in human plasma. In this paper, the PEA principle was applied to the detection of procalcitonin (PCT), a widely used biomarker for the identification of bacterial infection. A simple, short PEA protocol, with an assay time suitable for point-of-care diagnostics, is presented here as a proof of concept. Pairs of oligonucleotides and monoclonal antibodies were selected to generate tools specifically adapted to the development of an efficient PEA for PCT detection. The assay time was reduced by more than 13-fold compared to published versions of PEA, without significantly affecting assay performance. It was also demonstrated that T4 DNA polymerase could advantageously be replaced by other polymerases having strong 3’>5’ exonuclease activity. The sensitivity of this improved assay was determined to be about 0.1 ng/mL of PCT in plasma specimen. The potential use of such an assay in an integrated system for the low-plex detection of biomarkers in human specimen at the point of care was discussed.

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Targeted multiplex proteomics for prediction of all-cause mortality during long-term follow-up in outpatients with peripheral arterial disease

Cited by 6 publications

References 36 publications

Are the results from a multiplex proteomic assay and a conventional immunoassay for NT-proBNP and GDF-15 comparable?

Are the results from a multiplex proteomic assay and a conventional immunoassay for NT-proBNP and GDF-15 comparable?

Circulating Biomarkers in Lower Extremity Artery Disease

Procalcitonin detection in human plasma specimens using a fast version of proximity extension assay

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