ArticleBlood2020
Fc-modified HIT-like monoclonal antibody as a novel treatment for sepsis.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- PF4 drives mechanical overload-induced temporomandibular joint osteoarthritis through TLR2-dependent activation of NF-κB.Journal of translational medicine · 2026Article
- Target degradation of CASPASE-1 for alleviation of inflammation in sepsisActa pharmaceutica Sinica. B · 2026Article
- Platelet factor 4 in cognitive, immune and hematopoietic aging: emerging evidence and translational challenges.Frontiers in immunology · 2026Review
- Antiphospholipid syndrome (APS) is a platelet factor 4 (PF4)-centric immunothrombotic disorder.bioRxiv : the preprint server for biology · 2025Article
- Platelet factor 4 modulates endothelial cell antimicrobial activity to enhance bacterial clearance and improve sepsis outcomes.bioRxiv : the preprint server for biology · 2025Article
- Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.Infection and immunity · 2025Review
- Association Between Neutrophil Percentage-to-Albumin Ratio and Periodontitis: A Cross-Sectional Study.International dental journal · 2025Article
- Platelet Factor 4: A Mysterious Chemokine in Inflammatory Regulation Diseases.Journal of inflammation research · 2025Review
- Inhibitors of Polyphosphate and Neutrophil Extracellular Traps.Seminars in thrombosis and hemostasis · 2024Review
- Targeting neutrophil extracellular trap accumulation under flow in patients with immune-mediated thrombotic thrombocytopenic purpura.Blood advances · 2024Article
- Beyond anti-inflammatory strategies: addressing immunosuppression with nanomaterials in sepsis treatment.Frontiers in immunology · 2024Article
- Platelet factor 4 limits neutrophil extracellular trap- and cell-free DNA-induced thrombogenicity and endothelial injury.JCI insight · 2023Article
- Treatment of thrombocytopenia and thrombosis in HIT in mice using deglycosylated KKO: a novel therapeutic?Blood advances · 2023Article
- Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation.Research and practice in thrombosis and haemostasis · 2023Article
- Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation.International journal of nanomedicine · 2023Review
- Platelet factor 4 improves survival in a murine model of antibiotic-susceptible and methicillin-resistantFrontiers in cellular and infection microbiology · 2023Article
- Chemokines, molecular drivers of thromboinflammation and immunothrombosis.Frontiers in immunology · 2023Review
- Role of Acute Thrombosis in Coronavirus Disease 2019.Critical care clinics · 2022Review
- The Impact of Cytokines on Neutrophils' Phagocytosis and NET Formation during Sepsis-A Review.International journal of molecular sciences · 2022Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Sepsis is characterized by multiorgan system dysfunction that occurs because of infection. It is associated with high morbidity and mortality and is in need of improved therapeutic interventions. Neutrophils play a crucial role in sepsis, releasing neutrophil extracellular traps (NETs) composed of DNA complexed with histones and toxic antimicrobial proteins that ensnare pathogens, but also damage host tissues. At presentation, patients often have a significant NET burden contributing to the multiorgan damage. Therefore, interventions that inhibit NET release would likely be ineffective at preventing NET-based injury. Treatments that enhance NET degradation may liberate captured bacteria and toxic NET degradation products (NDPs) and likely be of limited therapeutic benefit as well. We propose that interventions that stabilize NETs and sequester NDPs may be protective in sepsis. We showed that platelet factor 4 (PF4), a platelet-associated chemokine, binds and compacts NETs, increasing their resistance to DNase I. We now show that PF4 increases NET-mediated bacterial capture, reduces the release of NDPs, and improves outcome in murine models of sepsis. A monoclonal antibody KKO which binds to PF4-NET complexes, further enhances DNase resistance. However, the Fc portion of this antibody activates the immune response and increases thrombotic risk, negating any protective effects in sepsis. Therefore, we developed an Fc-modified KKO that does not induce these negative outcomes. Treatment with this antibody augmented the effects of PF4, decreasing NDP release and bacterial dissemination and increasing survival in murine sepsis models, supporting a novel NET-targeting approach to improve outcomes in 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.