ArticleCellular & molecular immunology2021
Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases.
Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 142 citations in OpenAlex.
- NLRX1 is a critical neutrophil checkpoint modulating ferroptosis and suppressing NETosis to attenuate joint damage in arthritis.Cell death and differentiation · 2026Article
- Phenotypic switching of gastrointestinal smooth muscle cells and the regulatory role of macrophages: a literature review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Protective and Pathogenic Antibodies to Citrullinated Antigens.Immunological reviews · 2026Review
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Turmeric-derived nanovesicles reprogram pathological NETosis to mitigate inflammatory bone loss.Journal of nanobiotechnology · 2026Article
- Phase I trial in participants with rheumatoid arthritis and healthy volunteers with CIT-013, a first-in-class extracellular traps targeted therapy.EULAR rheumatology open · 2026Article
- New Insights Into the Role of Neutrophils in Lymphoma.Cancer medicine · 2026Review
- Review
- Beyond PAD Inhibition: Emerging Avenues and Natural Products for Targeting Citrullination in Immune Diseases.Biomedicines · 2026Review
- Inflammaging-induced TRAF3 degradation impairs AMP biosynthesis to drive sarcopenia.Research square · 2026Article
- Targeting Neutrophil Function as Therapy for Hidradenitis Suppurativa.International journal of molecular sciences · 2026Review
- Role of neutrophils in regulating vascular permeability in inflammatory and autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Neutrophils as critical orchestrators of chronic inflammation.Cellular & molecular immunology · 2026Review
- Antibody-opsonized extracellular traps modulate macrophage responses and attenuate their T cell-associated inflammatory and costimulatory characteristics.Frontiers in immunology · 2026Article
- Revisiting B-cell targeted therapies in rheumatoid arthritis: from paradoxical biology to deep immune reset.Frontiers in immunology · 2026Review
- Study on the pro-inflammatory injury of neutrophil extracellular traps in gouty nephropathy.Frontiers in immunology · 2026Review
- Molecular basis of post-translational neoantigen generation in rheumatoid arthritis: breaking immunological tolerance and implications for targeted therapy.Frontiers in immunology · 2026Review
- Review
- Neutrophil Extracellular Traps (NETs) as a Potential Target for Anti-Aging: Role of Therapeutic Apheresis.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2025Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive release of neutrophil extracellular traps (NETs) is associated with disease severity and contributes to tissue injury, followed by severe organ damage. Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models, indicating that NETs are potential therapeutic targets. Here, we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody (tACPA) has broad therapeutic potential. Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology, including inflammatory arthritis (IA), pulmonary fibrosis, inflammatory bowel disease and sepsis. We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention, whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects. Because citrullinated histones are generated during NET release, we investigated the ability of tACPA to inhibit NET formation. tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli. Moreover, tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo, which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA. To our knowledge, we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases, as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner.
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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.