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Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and
Yuzi Tian1,2, Rachel M Russo1, Yongqing Li3
1Department of Surgery, University of Michigan Health System, University of Michigan Medical School, 1500 E Medical Center Dr. SPC 5331, Ann Arbor, MI, 48109-5331, USA.
Purpose:
Microbial infection stimulates neutrophil/macrophage/monocyte extracellular trap formation, which leads to the release of citrullinated histone H3 (CitH3) catalyzed by peptidylarginine deiminase (PAD) 2 and 4. Understanding these molecular mechanisms in the pathogenesis of septic shock will be an important next step for developing novel diagnostic and treatment modalities. We sought to determine the expression of CitH3 in patients with septic shock, and to correlate CitH3 levels with PAD2/PAD4 and clinically relevant outcomes.
Methods:
Levels of CitH3 were measured in serum samples of 160 critically ill patients with septic and non-septic shock, and healthy volunteers. Analyses of clinical and laboratory characteristics of patients were conducted.
Results:
Levels of circulating CitH3 at enrollment were significantly increased in septic shock patients (n = 102) compared to patients hospitalized with non-infectious shock (NIC) (n = 32, p < 0.0001). The area under the curve (95% CI) for distinguishing septic shock from NIC using CitH3 was 0.76 (0.65-0.86). CitH3 was positively correlated with PAD2 and PAD4 concentrations and Sequential Organ Failure Assessment Scores [total score (r = 0.36, p < 0.0001)]. The serum levels of CitH3 at 24 h (p < 0.01) and 48 h (p < 0.05) were significantly higher in the septic patients that did not survive.
Conclusion:
CitH3 is increased in patients with septic shock. Its serum concentrations correlate with disease severity and prognosis, which may yield vital insights into the pathophysiology of sepsis.
Insights
Levels of citrullinated histone H3 (CitH3) are elevated in septic shock patients, correlating with disease severity and poor prognosis. This finding offers insights into sepsis pathophysiology and potential diagnostic markers.
Area of Science:
- Biochemistry
- Immunology
- Critical Care Medicine
Background:
- Microbial infections trigger extracellular trap formation by immune cells, releasing citrullinated histone H3 (CitH3).
- Peptidylarginine deiminase (PAD) 2 and 4 enzymes catalyze CitH3 formation.
- Understanding these mechanisms is crucial for developing diagnostics and treatments for septic shock.
Purpose of the Study:
- To determine CitH3 expression in septic shock patients.
- To correlate CitH3 levels with PAD2/PAD4 expression.
- To assess the relationship between CitH3 and clinical outcomes in septic shock.
Main Methods:
- Serum samples from 160 critically ill patients (septic shock, non-infectious shock) and healthy volunteers were analyzed for CitH3 levels.
- Clinical and laboratory characteristics of patients were assessed.
- CitH3 levels were correlated with PAD2/PAD4 concentrations and Sequential Organ Failure Assessment (SOFA) scores.
Main Results:
- Septic shock patients exhibited significantly higher circulating CitH3 levels compared to non-infectious shock patients.
- CitH3 levels positively correlated with PAD2, PAD4, and SOFA scores.
- Elevated CitH3 levels at 24 and 48 hours were associated with non-survival in septic patients.
Conclusions:
- CitH3 is significantly increased in patients with septic shock.
- Serum CitH3 concentrations correlate with disease severity and prognosis in sepsis.
- CitH3 may provide valuable insights into sepsis pathophysiology and serve as a potential biomarker.
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