ReviewJournal of thrombosis and haemostasis : JTH2021
PAD4 takes charge during neutrophil activation: Impact of PAD4 mediated NET formation on immune-mediated disease.
Review in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mitochondria: a breakthrough in combating rheumatoid arthritis.Frontiers in medicine · 2024Pooled it
- Autoantibodies and T Cells Target Citrullinated and Homocitrullinated Antigens in Rheumatoid Arthritis.Immunological reviews · 2026Review
- Recent Advances in Fluorescent Probes for Imaging Enzyme Activity in NETosis.Chembiochem : a European journal of chemical biology · 2026Review
- Dual Targeting of Net Formation and Coagulation Improves Survival and Organ Protection in Experimental Sepsis.Shock (Augusta, Ga.) · 2026Article
- Regulated cell death-induced coagulation dysfunction in sepsis.Journal of thrombosis and thrombolysis · 2026Review
- HypervirulentMicrobiology spectrum · 2026Article
- Persistent NET states link lesion-related microbial signals to the cold tumor-related local restrictive environment: a context-dependent working model.Cell communication and signaling : CCS · 2026Review
- Neutrophil extracellular traps (NETosis) in gynecologic cancers: from pathogenesis to therapeutic opportunities: a narrative review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Research progress on neutrophil extracellular traps in sepsis‑induced coagulopathy (Review).Molecular medicine reports · 2026Review
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Nature meets immunity: curcumin's role in modulating neutrophil extracellular traps.Inflammopharmacology · 2026Review
- Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Role of histone modifications in gastric cancer (Review).International journal of oncology · 2026Review
- Substantially Altered Local and Systemic Immunity in Ischemia-Free Versus Conventional Liver Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Natural Products Targeting PAD4 in NETosis: Structural and Mechanistic Insights into Direct and Indirect Inhibition.Biomolecules · 2026Review
- NCX1 reverse mode promotes calcium-dependent Neutrophil Extracellular Trap formation and lung damage in chronic obstructive pulmonary disease.Nature communications · 2026Article
- The Neutrophil-NET Axis in Immune Checkpoint Inhibitor Resistance in Non-Small Cell Lung Cancer: Roles, Biomarkers and Therapeutic Opportunities.Biomolecules · 2026Review
- Profiling Protein Citrullination in Extracellular Vesicles by Single-Molecule Detection Using Direct Stochastic Optical Reconstruction Microscopy.Journal of biophotonics · 2026Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPeptidyl arginine deiminase 4 (PAD4) is an enzyme that converts arginine into citrulline. PAD4 is expressed in neutrophils that, when activated, can drive the formation of neutrophil extracellular traps (NETs). Uncontrolled activation of PAD4 and subsequent citrullination of proteins is increasingly recognized as a driver of (auto)immune diseases. Currently, our understanding of PAD4 structure-function relationships and activity control in vivo is incomplete.
aimsTo provide the current state-of-the-art on PAD4 structure-activity relationships and involvement of PAD4 in autoimmune disorders as well as in thrombo-inflammatory disease. MATERIALS &
methodsLiterature review and molecular modelling Results: In this review, we used molecular modelling to generate a three-dimensional structure of the complete PAD4 molecule. Using our model, we discuss the catalytic conversion of the arginine substrate to citrulline. Besides mechanistic insight into PAD4 function, we give an overview of biological functions of PAD4 and mechanisms that influence its activation. In addition, we discuss the crucial role of PAD4-mediated citrullination of histones during the formation of NETs. Subsequently, we focus on the role of PAD4-mediated NET formation and its role in pathogenesis of rheumatoid arthritis, sepsis and (immune-)thrombosis. Finally, we summarize current efforts to design different classes of PAD4 inhibitors that are being developed for improved treatment of autoimmune disorders as well as thrombo-inflammatory disease. DISCUSSION: Advances in PAD4 structure-function are still necessary to gain a complete insight in mechanisms that control PAD4 activity in vivo. The involvement of PAD4 in several diseases signifies the need for a PAD4 inhibitor. Although progress has been made to produce an isotype specific and potent PAD4 inhibitor, currently no PAD4 inhibitor is ready for clinical use.
conclusionMore research into PAD4 structure and function and into the regulation of its activity is required for the development of PAD4 specific inhibitors that may prove vital to combat and prevent autoimmune disorders and (thrombo)inflammatory disease.
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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.