ArticleArthritis research & therapy2021
Anti-peptidylarginine deiminase-4 antibodies at mucosal sites can activate peptidylarginine deiminase-4 enzyme activity in rheumatoid arthritis.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- New Frontiers in Autoimmune Diagnostics: A Systematic Review on Saliva Testing.International journal of environmental research and public health · 2023Pooled it
- Novel Biomarker for Rheumatoid Arthritis: Serum Peptidylarginine Deiminase 4-Potentiating Activity in an Anti-Citrullinated Protein Antibody-Positive At-Risk Population.Scandinavian journal of immunology · 2026Article
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Glycosaminoglycans activate peptidylarginine deiminase 4 by enhancing calcium affinity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024Review
- Inflammatory Arthritis After COVID-19: A Case Series.The American journal of case reports · 2023Article
- Serum antibodies to peptidylarginine deiminase-4 in rheumatoid arthritis associated-interstitial lung disease are associated with decreased lung fibrosis and improved survival.The American journal of the medical sciences · 2023Article
- Inhalant and Additional Mucosal-Related Environmental Risks for Rheumatoid Arthritis.Rheumatic diseases clinics of North America · 2022Review
- Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Anti-Protein-Arginine Deiminase 4 IgG and IgA Delineate Severe Rheumatoid Arthritis.Diagnostics (Basel, Switzerland) · 2022Article
- Detection of Autoantibodies in Saliva as New Avenue for the Diagnosis and Management of Autoimmune Patients.Diagnostics (Basel, Switzerland) · 2022Article
- The lack of association between PADI4_94 or PADI4_104 polymorphisms and RF, ACPA and anti-PAD4 in patients with rheumatoid arthritis.Scientific reports · 2022Article
- The virtues and vices of protein citrullination.Royal Society open science · 2022Review
- A Roadmap for Investigating Preclinical Autoimmunity Using Patient-Oriented and Epidemiologic Study Designs: Example of Rheumatoid Arthritis.Frontiers in immunology · 2022Review
- Crosstalk between B cells and neutrophils in rheumatoid arthritis.Immunology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMucosal sites are hypothesized to play a role in the development of rheumatoid arthritis (RA). Since serum anti-peptidylarginine deiminase (PAD)4 antibodies, including a subset that cross-react with PAD3 (PAD3/4), are specific for RA and associate with severe disease, we sought to examine whether anti-PAD4 and anti-PAD3/4 antibodies were present in the lung and oral mucosa of subjects with RA and "at-risk" for RA.
methodsWe included 37 RA, 25 healthy control, and 46 subjects "at-risk" for RA based on familial RA and/or serum anti-citrullinated protein antibody (ACPA) positivity. Paired serum, sputum, and saliva were evaluated for anti-PAD4 and anti-PAD3/4 using immunoprecipitation and ACPA using ELISA. Immunoglobulins (Ig) were purified from representative samples, and their effect on citrullination of histone H3 by recombinant human PAD4 was measured by anti-citH3 immunoblot.
resultsAnti-PAD4 antibodies were detected in the serum of 6/37 (16.2%), sputum of 3/37 (8.1%), and saliva of 3/33 (9.1%) RA subjects and in the serum and sputum of 1/46 (2.2%) at-risk subjects. None of the healthy controls had anti-PAD4 antibodies at any site. Serum, sputum, and salivary anti-PAD4 antibodies were more prevalent in RA subjects with RA duration >2 years. Purified antibodies from representative anti-PAD4-positive and anti-PAD3/4-positive sputum were primarily of the IgA isotype and able to increase PAD4 enzymatic activity.
conclusionsAnti-PAD4 antibodies are present in the sputum and saliva of a portion of RA patients and are infrequent in at-risk subjects. Importantly, the ability of anti-PAD4, and particularly anti-PAD3/4, antibodies in the sputum to enhance PAD4 enzymatic activity suggests that anti-PAD4 may play an active role in the RA lung.
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