Increased plasma nucleosomes are associated with severe sepsis in foals.
Abstract: Sepsis is a main cause of death in neonatal foals. While the syndrome is not completely understood, sepsis is a dysregulated inflammatory response of the host to infection. It can be difficult to diagnose because of varying and non-specific clinical signs and imperfect diagnostic tests. Increased circulating nucleosome levels have been detected in humans and animals with sepsis, but this has not been documented in foals. Nucleosomes are released extracellularly during neutrophil extracellular trap formation, as well as from damaged and dead cells. We analysed plasma samples from clinically healthy (n = 16), sick non-septic (n = 31) and septic (n = 36) foals using an enzyme-linked immunosorbent assay (ELISA) that targeted nucleosomes. Septic foals with evidence of hypoperfusion and/or organ dysfunction were classified as severe sepsis (n = 24). The main objective was to determine if nucleosome levels were increased in foals with sepsis, particularly those with severe sepsis. Our data identified that nucleosome levels in foals with severe sepsis on the day of study entry were increased significantly compared to all other foals. There was not a significant difference in nucleosome levels between sick non-septic or clinically healthy foals. Foal groups were not age-matched and factors associated with the clinical nature of the study may have affected the results. Further research with larger numbers of foals of similar ages, would be necessary to determine if the analysis of nucleosomes and related biomarkers are helpful adjuncts for the assessment and understanding of equine neonatal sepsis.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
Publication Date: 2025-01-09 PubMed ID: 39793919DOI: 10.1016/j.tvjl.2025.106297Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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Overview
- This study investigated whether plasma nucleosome levels are elevated in neonatal foals with sepsis, particularly in those with severe sepsis.
- The researchers found that foals with severe sepsis had significantly higher plasma nucleosome concentrations compared to healthy foals or those with non-septic illnesses.
Background
- Sepsis is a leading cause of death in newborn foals (neonatal foals).
- It is characterized by a dysregulated inflammatory response to infection, which can lead to widespread tissue damage and organ failure.
- Diagnosing sepsis in foals is challenging because clinical signs are variable and non-specific, and current diagnostic tests are not ideal.
- Nucleosomes are complexes of DNA and histone proteins released into the bloodstream during cell death and neutrophil extracellular trap (NET) formation.
- Increased circulating nucleosome levels have been observed in human and animal sepsis cases, but this had not been documented in foals before this study.
Objectives
- The main goal was to assess if plasma nucleosome levels are increased in foals with sepsis.
- Specifically, the study aimed to examine nucleosome concentrations in foals with severe sepsis, which includes those showing signs of hypoperfusion (inadequate blood flow) and/or organ dysfunction.
Methods
- Plasma samples were collected from three groups of foals:
- Clinically healthy foals (n = 16)
- Sick but non-septic foals (n = 31)
- Septic foals (n = 36), with 24 classified as severe sepsis
- Nucleosome levels were measured using an enzyme-linked immunosorbent assay (ELISA) specifically targeting nucleosomes.
- Classification of severe sepsis was based on evidence of hypoperfusion and/or organ dysfunction at the time of study entry.
Key Findings
- Foals with severe sepsis had significantly higher plasma nucleosome levels compared to:
- Healthy foals
- Sick non-septic foals
- Septic foals without severe symptoms
- There was no significant difference found in nucleosome levels between sick non-septic foals and clinically healthy foals.
Limitations
- Foal groups were not age-matched, which may influence nucleosome levels or disease susceptibility.
- Clinical study conditions and the variability inherent in naturally occurring cases could have affected the results.
- The relatively small sample sizes limit the statistical power of the study.
Conclusions and Future Directions
- Increased circulating nucleosomes may serve as a biomarker for severe sepsis in neonatal foals.
- Measurement of nucleosomes could potentially aid in the diagnosis and assessment of sepsis severity.
- Further studies with larger cohorts and age-matched foals are necessary to validate the diagnostic utility of nucleosome measurement.
- Future research should also explore related biomarkers to improve understanding and management of equine neonatal sepsis.
Cite This Article
APA
Birckhead EM, Raidal SL, Das S, Raidal SR.
(2025).
Increased plasma nucleosomes are associated with severe sepsis in foals.
Vet J, 309, 106297.
https://doi.org/10.1016/j.tvjl.2025.106297 Publication
Researcher Affiliations
- Gulbali Institute, School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science and Health, Charles Sturt University, Locked Bag 588, Booroma St, Wagga Wagga, NSW 2678, Australia. Electronic address: ebirckhead@csu.edu.au.
- Gulbali Institute, School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science and Health, Charles Sturt University, Locked Bag 588, Booroma St, Wagga Wagga, NSW 2678, Australia.
- Gulbali Institute, School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science and Health, Charles Sturt University, Locked Bag 588, Booroma St, Wagga Wagga, NSW 2678, Australia.
- Gulbali Institute, School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science and Health, Charles Sturt University, Locked Bag 588, Booroma St, Wagga Wagga, NSW 2678, Australia.
MeSH Terms
- Animals
- Horses
- Nucleosomes / metabolism
- Horse Diseases / blood
- Sepsis / veterinary
- Sepsis / blood
- Animals, Newborn
- Female
- Enzyme-Linked Immunosorbent Assay / veterinary
- Male
Conflict of Interest Statement
Declaration of Competing Interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper.
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