ArticleArthritis & rheumatology (Hoboken, N.J.)2014
Peptidylarginine deiminase 4 contributes to tumor necrosis factor α-induced inflammatory arthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Global research trends and focus on the link between rheumatoid arthritis and neutrophil extracellular traps: a bibliometric analysis from 1985 to 2023.Frontiers in immunology · 2023Pooled it
- Anti-gingipain antibodies and ACE1 activity in rheumatoid arthritis: associations with disease activity and cardiovascular comorbidity in a cross-sectional study.Rheumatology international · 2026Article
- PAD4 deletion in synovial macrophages exacerbates pathology in inflammatory arthritis.Research square · 2026Article
- Hub genes of neutrophil extracellular traps in abdominal aortic aneurysm: a bioinformatics analysis.Hereditas · 2026Article
- Epigenetic regulatory mechanisms of autoimmune skin diseases: novel biomarkers and therapeutic prospects.Clinical epigenetics · 2025Review
- Anti-Peptidylarginine Deiminase 4 Autoantibodies Derived From Patients With Rheumatoid Arthritis Exert Pathogenic Effects by Activating Monocytes and Exacerbating Inflammatory Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies.International journal of molecular sciences · 2024Article
- Macrophage extracellular traps require peptidylarginine deiminase 2 and 4 and are a source of citrullinated antigens bound by rheumatoid arthritis autoantibodies.Frontiers in immunology · 2024Article
- Review
- Citrullination of matrisomal proteins in health and diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Review
- Proteomic and Metabolomic Changes in Psoriasis Preclinical and Clinical Aspects.International journal of molecular sciences · 2023Review
- Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4.Scientific reports · 2023Article
- PAD4 silencing inhibits inflammation whilst promoting trophoblast cell invasion and migration by inactivating the NEMO/NF-κB pathway.Experimental and therapeutic medicine · 2022Article
- The Prominent Role of Hematopoietic Peptidyl Arginine Deiminase 4 in Arthritis: Collagen- and Granulocyte Colony-Stimulating Factor-Induced Arthritis Model in C57BL/6 Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses.Journal of immunology research · 2022Article
- Disease mechanisms in preclinical rheumatoid arthritis: A narrative review.Frontiers in medicine · 2022Review
- Emerging Roles of Post-Translational Modifications in Skin Diseases: Current Knowledge, Challenges and Future Perspectives.Journal of inflammation research · 2022Review
- Neutrophils in the Pathogenesis of Rheumatic Diseases: Fueling the Fire.Clinical reviews in allergy & immunology · 2021Review
- Tumor Necrosis Factor Induces Obliterative Pulmonary Vascular Disease in a Novel Model of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
objectivePeptidylarginine deiminase 4 (PAD4) is a citrullinating enzyme that has multiple associations with inflammation. In rheumatoid arthritis, PAD4 and protein citrullination are increased in inflamed joints, and anti-citrullinated protein antibodies (ACPAs) form against citrullinated antigens are formed. ACPA immune complexes can deposit in the joint and induce the production of tumor necrosis factor α (TNFα), a critical inflammatory cytokine in the pathogenesis of rheumatoid arthritis. Further, in other settings, TNFα has been shown to induce PAD4 activity and modulate antibody formation. We undertook this study to investigate whether TNFα and PAD4 may synergistically exacerbate autoantibody production and inflammatory arthritis.
methodsTo determine whether TNFα and PAD4 augment autoantibody production and inflammatory arthritis, we first used a multiplex assay to determine whether mice with chronic inflammatory arthritis due to overexpression of TNFα develop autoantibodies against native and citrullinated antigens. With TNF(+) PAD4(+/+) and TNF(+) PAD4(-/-) mice, we then compared serum autoantibody levels by multiplex array, lymphocyte activation by flow cytometry, total serum IgG levels by enzyme-linked immunosorbent assay, arthritis by clinical and histologic scoring, and systemic inflammation using microfluidic devices.
resultsTNFα-overexpressing mice had increased levels of autoantibodies reactive against native and citrullinated antigens. PAD4(-/-) mice with TNFα-induced arthritis had lower levels of autoantibodies reactive against native and citrullinated antigens, decreased T cell activation and total IgG levels, and reduced inflammation and arthritis compared to PAD4(+/+) TNFα-overexpressing mice.
conclusionPAD4 mediates autoantibody production and inflammatory arthritis downstream of TNFα.
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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.