ArticleArthritis research & therapy2014
Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen.
Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
51 citing papers in PubMed, 80 citations in OpenAlex.
- S100A11 (calgizzarin) is released via NETosis in rheumatoid arthritis (RA) and stimulates IL-6 and TNF secretion by neutrophils.Scientific reports · 2021Trial
- Discovery of Post-Translationally Modified Epitopes in Autoimmunity: Someone Has to Fish so Everyone Can Eat.Immunological reviews · 2026Review
- NLRP3 inflammasome promotes PAD2/PAD4 release and protein citrullination in rheumatoid arthritis.Communications biology · 2026Article
- Inhibition of <italic>Pseudomonas aeruginosa</italic> Biofilm Formation by Peptidyl-Arginine Deiminases 2 and 4.Journal of innate immunity · 2026Article
- Hydrogen sulphide modifies the therapeutic potential of bone marrow mesenchymal stem cells in an adjuvant-induced polyarthritis rat model through the mitigation of angiogenesis, ectopic lymphoid tissue formation, and osteoclastogenesis.Inflammopharmacology · 2026Article
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- The monocyte cell surface is a unique site of autoantigen generation in rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- An unbiased proteomic analysis of PAD4 in human monocytes: novel substrates, binding partners and subcellular localizations.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Peptidylarginine deiminase 2 plays a key role in osteogenesis by enhancing RUNX2 stability through citrullination.Cell death & disease · 2023Article
- Article
- Microbial pathways to subvert host immunity generate citrullinated neoantigens targeted in rheumatoid arthritis.Current opinion in structural biology · 2022Review
- Pediatric Brain Tumors: Signatures from the Intact Proteome.International journal of molecular sciences · 2022Article
- Redox-Mediated Carbamylation As a Hapten Model Applied to the Origin of Antibodies to Modified Proteins in Rheumatoid Arthritis.Antioxidants & redox signaling · 2022Review
- Characterization and use of the ECV304 autoantigenic citrullinome to understand anti-citrullinated protein/peptide autoantibodies in rheumatoid arthritis.Arthritis research & therapy · 2022Article
- Genetic basis of defects in immune tolerance underlying the development of autoimmunity.Frontiers in immunology · 2022Review
- Citrullinated glucose-regulated protein 78 is a candidate target for melanoma immunotherapy.Frontiers in immunology · 2022Article
- The role of SERPIN citrullination in thrombosis.Cell chemical biology · 2021Article
- Crosstalk between B cells and neutrophils in rheumatoid arthritis.Immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMembers of the peptidylarginine deiminase (PAD) family catalyse the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients.
methodsAn enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined.
resultsApproximately 150 times lower levels of recombinant human PAD2 (rhPAD2) than of rhPAD4 were required for citrullination of fibrinogen. PAD activity was detected in four of five synovial fluid samples from RA patients and correlated with PAD2 concentrations in the samples (r = 0.98, P = 0.003). The calcium requirement for half-maximal activities of PAD2 and PAD4 were found in a range from 0.35 to 1.85 mM, and synovial fluid was found to contain sufficient calcium levels for the citrullination process to occur.
conclusionsWe present an assay with high specificity for PAD2 activity and show that citrullination of fibrinogen can occur in cell-free synovial fluid from RA patients.
Indexed as
Identifiers
What OpenQuestion holds
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.