ArticleInfection2021
Serum citrullinated histone H3 concentrations differentiate patients with septic verses non-septic shock and correlate with disease severity.
Article in Infection, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 3 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- New trends and hotspots in sepsis-related protein post-translational modification: a bibliometric and visual analysis.Frontiers in medicine · 2025Pooled it
- Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification.Cell death & disease · 2023Pooled it
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- The "Double-Edged Sword" of Neutrophils in Trauma: From Pathophysiological Mechanisms to Precision Immunomodulation Strategies.International journal of molecular sciences · 2026Review
- Article
- Role of post-translational modifications in modulating histone reactivity in the extracellular environment.Biochemical Society transactions · 2026Review
- Epigenetic regulation of neutrophil dysfunction in sepsis: mechanisms, biomarkers, and translational challenges.Journal of translational medicine · 2026Review
- Post-treatment with H12-(ADP)-liposomes after LPS challenge ameliorated coagulopathy and critical organ injury in rats.Intensive care medicine experimental · 2026Article
- Serum citrullinated histone H3 as a biomarker of disease activity and renal outcome in microscopic polyangiitis and granulomatosis with polyangiitis.Arthritis research & therapy · 2026Article
- Current Insights into Clinical, Molecular, and Therapeutic Approaches to Acute Respiratory Distress Syndrome.Medical sciences (Basel, Switzerland) · 2026Review
- Citrullinated histone H3 and procalcitonin in the diagnosis and predicting the outcome of septic shock.BMC infectious diseases · 2026Article
- High-mobility group box 1 protein, histone H3 and histone H4 are not associated with peripheral hypoperfusion in sepsis: a retrospective cohort study.Einstein (Sao Paulo, Brazil) · 2026Article
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Review
- Circulating NET Biomarkers as Predictors of Inflammatory Storm Escalation and Critical Illness in COVID-19.Journal of microbiology and biotechnology · 2025Article
- Emodin Alleviates Sepsis-Induced Multiorgan Damage by Inhibiting NETosis through Targeting Neutrophils BCL-10.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inflammatory neutrophil responses and T cell activation in ART-treated SIVmac239-infected rhesus macaques.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- A citrullinated histone H3 monoclonal antibody for immune modulation in sepsis.Nature communications · 2025Article
- CitH3, a Druggable Biomarker for Human Diseases Associated with Acute NETosis and Chronic Immune Dysfunction.Pharmaceutics · 2025Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeMicrobial 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.
methodsLevels 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.
resultsLevels 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.
conclusionCitH3 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.