Concentrations of Plasma Nucleosomes but Not Cell-Free DNA Are Prognostic in Dogs Following Trauma

Letendre, Jo‐Annie; Goggs, Robert

doi:10.3389/fvets.2018.00180

Cited by 23 publications

(25 citation statements)

References 46 publications

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“…This is significantly lower than the concentration seen in the dogs with lymphoma reported in this study with median of 590 ng/mL. Comparisons between the concentrations of nucleosomes reported here and those in other reports of inflammation and control groups are difficult due to the fact that nucleosome concentrations have previously been reported only in arbitrary units(7)(8)(9)(20)(21)(22).…”

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confidence: 80%

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Wilson-Robles

Miller

Jarvis

et al. 2020

Preprint

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AbstractIntroductionNucleosomes consist of small fragments of DNA wrapped around a histone octamer core. Diseases such as cancer or inflammation lead to cell death, which causes fragmentation and release of nucleosomes into the blood. The Nu.Q™ technology measures circulating nucleosome levels and exploits the different compositions of cancer derived nucleosomes in blood to detect and identify cancer even at early stages. The objectives of this study are to identify the optimal sample type for the Nu.Q™ H3.1 assay and to determine if it can accurately detect nucleosomes in the blood of healthy canines as well as those with cancer.Materials and MethodsBlood samples from healthy canine volunteers as well as dogs newly diagnosed with lymphoma were used. The blood was processed at a variety of times under a variety of conditions to determine the most reliable sample type and conditions, and to develop an appropriate processing strategy to ensure reliably accurate results.ResultsNucleosomes could be detected using a variety of sample collection and processing protocols. Nucleosome signals were highest in EDTA plasma and serum samples and most consistent in plasma. Samples should be processed within an hour of collection. Experiments showed that samples were able to withstand several freeze thaw cycles. Processing time and tcollection tube type did affect nucleosome detection levels. Finally, significantly elevated concentrations of nucleosomes were seen in a small cohort of dogs that had been newly diagnosed with lymphoma.ConclusionsWhen samples are collected and processed appropriately, the Nu.Q™ platform can reliably detect nucleosomes in the plasma of dogs. Further testing is underway to validate and optimize the Nu.Q™ platform for veterinary use.

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contrasting

confidence: 80%

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Wilson-Robles

Miller

Jarvis

et al. 2020

Preprint

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“…The lack of correlation between the two biomarker concentrations suggests that the cfDNA assay may be relatively insensitive to the nucleosomes in these plasma samples, as has been previously reported 41. In studies of other canine patient populations, these biomarkers have been determined to be positively correlated,19 20 but the strength of the association in those studies was weak. These weak associations may indicate related but distinct origins for release of these biomarkers and suggests that measuring both biomarkers may be worthwhile.…”

Section: Discussionmentioning

confidence: 73%

“…People with septic shock have significantly higher nucleosome concentrations than those with sepsis or fever,34 and plasma nucleosome concentrations correlate with organ dysfunction severity in septic critically ill people 36. Nucleosome concentrations are increased in horses with colic,37 in dogs with sepsis,19 21 and in dogs following trauma, where they correlate with injury severity and prognosis 20. Nucleosome concentrations are also increased in dogs with IMHA,24 38 a condition in which there may be a link between NETs and thrombosis 39.…”

Section: Introductionmentioning

confidence: 99%

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Effect of sample type on plasma concentrations of cell‐free DNA and nucleosomes in dogs

Goggs

2019

Veterinary Record Open

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Cell-free DNA (cfDNA) and nucleosomes are two biomarkers of cell death and neutrophil extracellular trap formation that are increased in dogs with sepsis, immune-mediated haemolytic anaemia, cancer and following trauma and have diagnostic and prognostic values. cfDNA and nucleosomes are typically measured in plasma samples using DNA-specific fluorophores and ELISA assays, respectively, but their concentrations may be affected by pre-analytical variables such as sample type. The present study aimed to investigate the influence of sample type on the plasma cfDNA and nucleosome concentrations of a heterogeneous group of dogs presenting to an emergency room. Triplicate samples were collected into K2-ethylenediamine tetraacetic acid, 3.2% citrate and a specialised DNA stabilisation tube (Streck BCT), processed rapidly and frozen for batch analysis. Biomarker concentrations were compared between sample types by calculation of Spearman’s correlation coefficients, and with Deming regression, Bland-Altman plots and the Friedman test. Overall, biomarker concentrations were highly correlated between the three sample types. The most concordant results were obtained using citrate samples and the DNA stabilisation tube. Matched cfDNA concentrations between the different sample types were significantly different but there was no significant difference between the nucleosome concentrations in any of the sample types. The present study suggests that cfDNA and nucleosomes can be successfully measured in various sample types, but distinct sample types do not produce interchangeable results. This argues for use of a consistent sample type within studies and suggests standardisation may be useful for the field.

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“…While nucleosomes are present in all mammalian cells, they can also be detected circulating in blood, where they are most commonly released by activated or dying white blood cells [5,6]. Large numbers of nucleosomes are released into the blood of humans and animals suffering from severe inflammation or trauma [7][8][9]. These small cell free (cf) DNA molecules have been shown to have immunostimulatory roles that differ from that of free circulating histones or double stranded cell free DNA(ds-cfDNA) [10].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

et al. 2020

View full text Add to dashboard Cite

Introduction Nucleosomes consist of small fragments of DNA wrapped around a histone octamer core. Diseases such as cancer or inflammation lead to cell death, which causes fragmentation and release of nucleosomes into the blood. The Nu.Q™ technology measures circulating nucleosome levels and exploits the different compositions of cancer derived nucleosomes in blood to detect and identify cancer even at early stages. The objectives of this study are to identify the optimal sample type for the Nu.Q™ H3.1 assay and to determine if it can accurately detect nucleosomes in the blood of healthy canines as well as those with cancer. Materials and methods Blood samples from healthy canine volunteers as well as dogs newly diagnosed with lymphoma were used. The blood was processed at a variety of times under a variety of conditions to determine the most reliable sample type and conditions, and to develop an appropriate processing strategy to ensure reliably accurate results. Results Nucleosomes could be detected using a variety of sample collection and processing protocols. Nucleosome signals were highest in EDTA plasma and serum samples and most consistent in plasma. Samples should be processed within an hour of collection. Experiments showed that samples were able to withstand several freeze thaw cycles. Processing time and tcollection tube type did affect nucleosome detection levels. Finally, significantly elevated concentrations of nucleosomes were seen in a small cohort of dogs that had been newly diagnosed with lymphoma. Conclusions When samples are collected and processed appropriately, the Nu.Q™ platform can reliably detect nucleosomes in the plasma of dogs. Further testing is underway to validate and optimize the Nu.Q™ platform for veterinary use.

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Concentrations of Plasma Nucleosomes but Not Cell-Free DNA Are Prognostic in Dogs Following Trauma

Cited by 23 publications

References 46 publications

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Effect of sample type on plasma concentrations of cell‐free DNA and nucleosomes in dogs

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

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