ArticleArthritis & rheumatology (Hoboken, N.J.)2017
High-Titer Rheumatoid Arthritis Antibodies Preferentially Bind Fibrinogen Citrullinated by Peptidylarginine Deiminase 4.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Ferrostatin-1 reduces the inflammatory response of rheumatoid arthritis by decreasing the antigen presenting function of fibroblast-like synoviocytes.Journal of translational medicine · 2025Article
- Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis.Frontiers in immunology · 2023Article
- Platelets derived citrullinated proteins and microparticles are potential autoantibodies ACPA targets in RA patients.Frontiers in immunology · 2023Article
- Redox-Mediated Carbamylation As a Hapten Model Applied to the Origin of Antibodies to Modified Proteins in Rheumatoid Arthritis.Antioxidants & redox signaling · 2022Review
- Identification of potential autoantigens in anti-CCP-positive and anti-CCP-negative rheumatoid arthritis using citrulline-specific protein arrays.Scientific reports · 2021Article
- Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy.BMC musculoskeletal disorders · 2021Article
- Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4.Frontiers in immunology · 2021Article
- Article
- Extracellular Vesicles and Post-Translational Protein Deimination Signatures in Mollusca-The Blue Mussel (Biology · 2020Article
- Anti-Citrullinated Protein Antibodies in Patients with Rheumatoid Arthritis: Biological Effects and Mechanisms of Immunopathogenesis.International journal of molecular sciences · 2020Review
- Generation of Distinct Patterns of Rheumatoid Arthritis Autoantigens by Peptidylarginine Deiminase Types 2 and 4 During Perforin-Induced Cell Damage.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- PAD enzymes in rheumatoid arthritis: pathogenic effectors and autoimmune targets.Nature reviews. Rheumatology · 2020Review
- Article
- Neutrophil Extracellular Traps Tied to Rheumatoid Arthritis: Points to Ponder.Frontiers in immunology · 2020Review
- CDK9 inhibitor CDKI-73 is synergetic lethal with PARP inhibitor olaparib in BRCA1 wide-type ovarian cancer.American journal of cancer research · 2020Article
- Detection of Citrullinated Fibrin in Plasma Clots of Rheumatoid Arthritis Patients and Its Relation to Altered Structural Clot Properties, Disease-Related Inflammation and Prothrombotic Tendency.Frontiers in immunology · 2020Article
- Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)-Novel insights into camelid immunity.Molecular immunology · 2020Article
- Autoantibodies to Peptidylarginine Deiminase 2 Are Associated With Less Severe Disease in Rheumatoid Arthritis.Frontiers in immunology · 2018Observational
- Rheumatoid arthritis and citrullination.Current opinion in rheumatology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveMost patients with rheumatoid arthritis (RA) harbor antibodies to citrullinated autoantigens such as citrullinated fibrinogen. Two isoforms of peptidylarginine deiminase (PAD), PAD type 2 (PAD2) and PAD4, which catalyze citrullination with different substrate specificities, can be detected in the synovium of RA patients. This study was undertaken to determine whether RA antibodies preferentially bind PAD2- or PAD4-citrullinated fibrinogen.
methodsRA patient and normal donor plasma specimens were tested for binding to PAD2- or PAD4-citrullinated fibrinogen, native fibrinogen, or citrullinated fibrinogen peptides in various dilutions by enzyme-linked immunosorbent assay (ELISA) and Western blotting. Bands corresponding to masses demonstrating RA antibody reactivity by Western blotting were excised and analyzed by mass spectrometry.
resultsAt low antibody titers (1:40 and 1:100), there was no significant difference between RA antibody reactivity to PAD2- and PAD4-citrullinated fibrinogen. When plasma was further diluted to 1:250 and 1:1,000, RA patient plasma bound PAD4-citrullinated fibrinogen significantly more than PAD2-citrullinated fibrinogen, as measured by ELISA and Western blotting. An increased antibody titer was associated with increased avidity for both PAD2- and PAD4-citrullinated fibrinogen. Both enzymes hypercitrullinated fibrinogen, but PAD4 citrullinated arginines more intermittently, generating a mix of citrullinated and noncitrullinated arginines. Peptide ELISA and preadsorption assays confirmed that the region of intermittent citrullination accounts for the majority of RA antibody binding to the β-chain of citrullinated fibrinogen.
conclusionAt high titers, RA antibodies preferentially bind fibrinogen modified by PAD4, because intermittent citrullination offers a more diverse assortment of citrullinated epitopes.
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