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High throughput urinary neopterin-to-creatinine ratio monitoring of systemic inflammation

High throughput urinary neopterin-to-creatinine ratio monitoring of systemic inflammation
High throughput urinary neopterin-to-creatinine ratio monitoring of systemic inflammation
BACKGROUND: Systemic inflammation is a marker of ill health and has prognostic implications in multiple health settings. Urinary neopterin is an excellent candidate as a non-specific marker of systemic inflammation. Expression as urinary neopterin-to-creatinine ratio (UNCR) normalizes for urinary hydration status. Major attractions include: (1) urine versus blood sampling, (2) integration of inflammation over a longer period compared to serum sampling, (3) high stability of neopterin and creatinine.

METHODS: A high-throughput ultra performance liquid chromatography - mass spectrometry method was developed to measure neopterin and creatinine together from the same urine sample. The assay was applied in several clinical scenarios: healthy controls, symptomatic infections and multiple sclerosis. Area-under-the-curve was compared between weekly and monthly sampling scenarios. Analysis of a single pooled sample was compared with averaging results from analysis of individual samples.

RESULTS: The assay has excellent intra-assay and inter-assay precision, linearity of dilution and spike-and-recovery. Higher UNCR was demonstrated in females versus males, older age, inflammatory disease (multiple sclerosis) and symptomatic infections. In healthy controls, fluctuations in inflammatory state also occurred in the absence of symptomatic infection or other inflammatory triggers. Analysis of a single pooled sample facilitates weekly urine sampling to integrate inflammatory activity over time.

CONCLUSIONS: UNCR is a useful biomarker of systemic inflammation. The method presented offer simplicity, speed, robustness, reproducibility, efficiency and proven utility in clinical scenarios. UNCR fluctuations underline the importance of longitudinal monitoring, versus a single time point, to capture a more representative estimate of an individual’s inflammatory state over time.
Stuart, Charlotte
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Zotova, Elina
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Koster, Grielof
e404c38a-6f48-430a-adf0-5208228cb9e7
Varatharaj, Aravinthan
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Richardson, Grace
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Cornick, Faye
956c961f-8e5d-446a-9a2a-8d133267f632
Weal, Mark
e8fd30a6-c060-41c5-b388-ca52c81032a4
Newman, Tracey
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Postle, Anthony
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Stuart, Charlotte
0db8a733-f236-4baa-955c-d6e147dc9387
Zotova, Elina
3558dd45-67a7-4e7a-b2ef-a9155ca784e8
Koster, Grielof
e404c38a-6f48-430a-adf0-5208228cb9e7
Varatharaj, Aravinthan
e65c9499-d9ad-4940-baba-76ed794176f8
Richardson, Grace
932094ac-97b9-4ec0-a00d-6ed9adba6194
Cornick, Faye
956c961f-8e5d-446a-9a2a-8d133267f632
Weal, Mark
e8fd30a6-c060-41c5-b388-ca52c81032a4
Newman, Tracey
322290cb-2e9c-445d-a047-00b1bea39a25
Postle, Anthony
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b

Stuart, Charlotte, Zotova, Elina, Koster, Grielof, Varatharaj, Aravinthan, Richardson, Grace, Cornick, Faye, Weal, Mark, Newman, Tracey, Postle, Anthony and Galea, Ian (2019) High throughput urinary neopterin-to-creatinine ratio monitoring of systemic inflammation. The Journal of Applied Laboratory Medicine. (In Press)

Record type: Article

Abstract

BACKGROUND: Systemic inflammation is a marker of ill health and has prognostic implications in multiple health settings. Urinary neopterin is an excellent candidate as a non-specific marker of systemic inflammation. Expression as urinary neopterin-to-creatinine ratio (UNCR) normalizes for urinary hydration status. Major attractions include: (1) urine versus blood sampling, (2) integration of inflammation over a longer period compared to serum sampling, (3) high stability of neopterin and creatinine.

METHODS: A high-throughput ultra performance liquid chromatography - mass spectrometry method was developed to measure neopterin and creatinine together from the same urine sample. The assay was applied in several clinical scenarios: healthy controls, symptomatic infections and multiple sclerosis. Area-under-the-curve was compared between weekly and monthly sampling scenarios. Analysis of a single pooled sample was compared with averaging results from analysis of individual samples.

RESULTS: The assay has excellent intra-assay and inter-assay precision, linearity of dilution and spike-and-recovery. Higher UNCR was demonstrated in females versus males, older age, inflammatory disease (multiple sclerosis) and symptomatic infections. In healthy controls, fluctuations in inflammatory state also occurred in the absence of symptomatic infection or other inflammatory triggers. Analysis of a single pooled sample facilitates weekly urine sampling to integrate inflammatory activity over time.

CONCLUSIONS: UNCR is a useful biomarker of systemic inflammation. The method presented offer simplicity, speed, robustness, reproducibility, efficiency and proven utility in clinical scenarios. UNCR fluctuations underline the importance of longitudinal monitoring, versus a single time point, to capture a more representative estimate of an individual’s inflammatory state over time.

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Accepted/In Press date: 15 July 2019

Identifiers

Local EPrints ID: 433516
URI: https://eprints.soton.ac.uk/id/eprint/433516
PURE UUID: c450a4af-cfc1-4165-8b95-da2811d9d36b
ORCID for Mark Weal: ORCID iD orcid.org/0000-0001-6251-8786
ORCID for Tracey Newman: ORCID iD orcid.org/0000-0002-3727-9258
ORCID for Anthony Postle: ORCID iD orcid.org/0000-0001-7361-0756
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 23 Aug 2019 16:30
Last modified: 24 Aug 2019 00:38

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Contributors

Author: Charlotte Stuart
Author: Elina Zotova
Author: Grielof Koster
Author: Aravinthan Varatharaj
Author: Grace Richardson
Author: Faye Cornick
Author: Mark Weal ORCID iD
Author: Tracey Newman ORCID iD
Author: Anthony Postle ORCID iD
Author: Ian Galea ORCID iD

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