ArticleEuropean journal of rheumatology2016
Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning.
Article in European journal of rheumatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Meta-analysis: diagnostic accuracy of the citrullinated peptides derived from fibrinogen and vimentin in rheumatoid arthritis.Clinical rheumatology · 2020Pooled it
- Citrullination Accompanies the Development of Carotid Atherosclerotic Plaques.Current medicinal chemistry · 2026Article
- GnRH Induces Citrullination of the Cytoskeleton in Murine Gonadotrope Cells.International journal of molecular sciences · 2024Article
- Review
- Molecular Factors in PAD2 (Cells · 2023Article
- The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications.International journal of molecular sciences · 2021Review
- Anti-citrullinated Protein Antibody Generation, Pathogenesis, Clinical Application, and Prospects.Frontiers in medicine · 2021Review
- Autoantibodies against a novel citrullinated fibrinogen peptide related to smoking status, disease activity and therapeutic response to methotrexate in cuban patients with early rheumatoid arthritis.Rheumatology international · 2020Article
- Identification and Characterization of the Lactating Mouse Mammary Gland Citrullinome.International journal of molecular sciences · 2020Article
- Technical comment on "Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis".Science immunology · 2020Article
- Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritis.Scientific reports · 2019Article
- Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer's disease.Journal of oral microbiology · 2018Review
- Carbamylation/citrullination of IgG Fc in bronchiectasis, established RA with bronchiectasis and RA smokers: a potential risk factor for disease.ERJ open research · 2017Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe molecular mechanism of citrullination involves the calcium-dependent peptidylarginine deiminase (PAD) family of enzymes. These enzymes induce a stereochemical modification of normal proteins and transform them into autoantigens, which in rheumatoid arthritis trigger a complex cascade of joint inflammatory events followed by chronic synovitis, pannus formation, and finally, cartilage destruction. By hypothesizing that PAD2 and PAD4 enzymes produce autoantigens, we investigated five possible synovial protein targets of PAD enzymes. MATERIAL AND
methodsWe measured PAD2, PAD4, and citrullinated proteins in 10 rheumatoid and 10 osteoarthritis synovial biopsies and then assessed the post-translational modifications of fibrinogen, cytokeratin, tubulin, IgG, and vimentin proteins using a double-fluorescence assay with specific antibodies and an affinity-purified anti-citrullinated peptide (CCP) antibody. The degree of co-localization was analyzed, and statistical significance was determined by ANOVA, Fisher's exact test, and regression analysis.
resultsThe principal results of this study demonstrated that citrullinated proteins, such as fibrinogen, IgG, and other probed proteins, were targets of PAD2 and PAD4 activity in rheumatoid synovial biopsies, whereas osteoarthritis biopsies were negative for this enzyme (p<0.0001). An analysis of citrullination sites using the UniProtKB/Swiss-Prot data bank predicts that the secondary structure of the analyzed proteins displays most of the sites for citrullination; a discussion regarding its possible meaning in terms of pathogenesis is made.
conclusionOur results support the conclusion that the synovial citrullination of proteins is PAD2 and PAD4 dependent. Furthermore, there is a collection of candidate proteins that can be citrullinated.
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