ArticlePloS one2018
Relative efficiencies of peptidylarginine deiminase 2 and 4 in generating target sites for anti-citrullinated protein antibodies in fibrinogen, alpha-enolase and histone H3.
Article in PloS one, 2018. 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.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- The TG2/LRP1 Pathway for T Cell Activation by Post-Translationally Modified Antigens.Immunological reviews · 2026Review
- NLRP3 inflammasome promotes PAD2/PAD4 release and protein citrullination in rheumatoid arthritis.Communications biology · 2026Article
- Roles of peptidylarginine deiminase (PAD) and protein citrullination in viral infections.Frontiers in microbiology · 2026Review
- Ferrostatin-1 reduces the inflammatory response of rheumatoid arthritis by decreasing the antigen presenting function of fibroblast-like synoviocytes.Journal of translational medicine · 2025Article
- A Multifaceted Computational Approach to Identify PAD4 Inhibitors for the Treatment of Rheumatoid Arthritis (RA).Metabolites · 2025Article
- A Gel-Based Proteomic Analysis Reveals Synovial α-Enolase and Fibrinogen β-Chain Dysregulation in Knee Osteoarthritis: A Controlled Trial.Journal of personalized medicine · 2023Article
- Autocitrullination confers monocyte chemotactic properties to peptidylarginine deiminase 4.Scientific reports · 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
- Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing on Citrullination, Carbamylation, and Acetylation.International journal of molecular sciences · 2021Review
- Identification of potential autoantigens in anti-CCP-positive and anti-CCP-negative rheumatoid arthritis using citrulline-specific protein arrays.Scientific reports · 2021Article
- Article
- Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4.Frontiers in immunology · 2021Article
- Peptidylarginine Deiminase 2 in Host Immunity: Current Insights and Perspectives.Frontiers in immunology · 2021Review
- Citrullination and PAD Enzyme Biology in Type 1 Diabetes - Regulators of Inflammation, Autoimmunity, and Pathology.Frontiers in immunology · 2021Review
- PAD enzymes in rheumatoid arthritis: pathogenic effectors and autoimmune targets.Nature reviews. Rheumatology · 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
- Identification of Novel Native Autoantigens in Rheumatoid Arthritis.Biomedicines · 2020Article
- Peptidyl Arginine Deiminase 2 (PADI2)-Mediated Arginine Citrullination Modulates Transcription in Cancer.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
objectivePeptidylarginine deiminase 2 (PAD2) and PAD4 are expressed in the synovium of rheumatoid arthritis (RA) patients and catalyze citrullination of arginine residues in proteins targeted by anti-citrullinated protein antibodies (ACPAs). Little is known about the relative importance of PAD2 and PAD4 in generating citrullinated self-antigens. Here we investigate the ability of PAD2 and PAD4 to generate citrullinated targets for ACPAs in four human proteins.
methodsSynovial fluid (SF) and plasma were collected from 42 RA patients. Human fibrinogen, human alpha-enolase (ENO1), human histone H3, and human serum albumin (HSA) were citrullinated in vitro by PAD2 or PAD4. The total degree of citrullination was determined using the anti-modified citrulline approach. Antibody binding to native and citrullinated proteins was measured by ELISA.
resultsACPAs within pooled SF from multiple RA patients reacted equally well with, and cross-reacted with, PAD2- and PAD4-citrullinated fibrinogen. ACPAs from most individual patient SF and plasma samples bound equally well to PAD2- and PAD4-citrullinated fibrinogen or ENO1. When histone H3 was used as target, PAD4 was generally superior in generating epitopes recognized by ACPAs. No binding to citrullinated HSA was observed.
conclusionIn most patients, PAD2 and PAD4 are equally efficient in generating citrullinated target sites for ACPAs in fibrinogen and ENO1. The binding of autoantibodies to histone H3 was generally higher after citrullination with PAD4 than with PAD2. Citrullinated HSA is not a target for ACPAs.
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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.