ArticleJournal of translational medicine2023
Validation of circulating histone detection by mass spectrometry for early diagnosis, prognosis, and management of critically ill septic patients.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Multifunctional Agarose-Based Biomaterials: From Tissue Engineering and Immunomodulation to Advanced Diagnostics and Translational Applications.Gels (Basel, Switzerland) · 2026Review
- Role of post-translational modifications in modulating histone reactivity in the extracellular environment.Biochemical Society transactions · 2026Review
- Short-Chain Fatty Acids: A Key Modulator of Sepsis-Associated Acute Respiratory Distress Syndrome.Journal of inflammation research · 2026Review
- Open chromatin-guided interpretable machine learning reveals cancer-specific chromatin features in cell-free DNA.Communications biology · 2025Article
- Circulating histones as clinical biomarkers in critically ill conditions.FEBS letters · 2025Review
- A phase I trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenously administered low-anticoagulant heparin (M6229) in critically ill sepsis patients.Intensive care medicine experimental · 2025Article
- Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients.Scientific reports · 2025Article
- Lactylation: a promising therapeutic target in ischemia-reperfusion injury management.Cell death discovery · 2025Review
- Endocytosis and non-canonical autophagy mediate extracellular histones cytotoxicity in vascular models of sepsis.Frontiers in immunology · 2025Article
- Clinical glycoproteomics: methods and diseases.MedComm · 2024Review
- Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review.Metabolites · 2024Review
- Sepsis-Induced Endothelial Dysfunction: Permeability and Regulated Cell Death.Journal of inflammation research · 2024Review
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs leading contributors to worldwide morbidity and mortality, sepsis and septic shock are considered a major global health concern. Proactive biomarker identification in patients with sepsis suspicion at any time remains a daunting challenge for hospitals. Despite great progress in the understanding of clinical and molecular aspects of sepsis, its definition, diagnosis, and treatment remain challenging, highlighting a need for new biomarkers with potential to improve critically ill patient management. In this study we validate a quantitative mass spectrometry method to measure circulating histone levels in plasma samples for the diagnosis and prognosis of sepsis and septic shock patients.
methodsWe used the mass spectrometry technique of multiple reaction monitoring to quantify circulating histones H2B and H3 in plasma from a monocenter cohort of critically ill patients admitted to an Intensive Care Unit (ICU) and evaluated its performance for the diagnosis and prognosis of sepsis and septic shock (SS).
resultsOur results highlight the potential of our test for early diagnosis of sepsis and SS. H2B levels above 121.40 ng/mL (IQR 446.70) were indicative of SS. The value of blood circulating histones to identify a subset of SS patients in a more severe stage with associated organ failure was also tested, revealing circulating levels of histones H2B above 435.61 ng/ml (IQR 2407.10) and H3 above 300.61 ng/ml (IQR 912.77) in septic shock patients with organ failure requiring invasive organ support therapies. Importantly, we found levels of H2B and H3 above 400.44 ng/mL (IQR 1335.54) and 258.25 (IQR 470.44), respectively in those patients who debut with disseminated intravascular coagulation (DIC). Finally, a receiver operating characteristic curve (ROC curve) demonstrated the prognostic value of circulating histone H3 to predict fatal outcomes and found for histone H3 an area under the curve (AUC) of 0.720 (CI 0.546-0.895) p < 0.016 on a positive test cut-off point at 486.84 ng/mL, showing a sensitivity of 66.7% and specificity of 73.9%.
conclusionsCirculating histones analyzed by MS can be used to diagnose SS and identify patients at high risk of suffering DIC and fatal outcome.
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