ArticleJournal of proteome research2017
Proteolysis by Granzyme B Enhances Presentation of Autoantigenic Peptidylarginine Deiminase 4 Epitopes in Rheumatoid Arthritis.
Article in Journal of proteome research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Anti-PAD4 antibodies link autoimmunity to PAD4 with CTL-associated rheumatoid arthritis.Annals of the rheumatic diseases · 2026Article
- Editorial: Roles of granzymes in inflammation, aging, and autoimmunity.Frontiers in immunology · 2025Article
- Granzyme B cleaves tenascin-C to release its C-terminal domain in rheumatoid arthritis.JCI insight · 2024Article
- The peculiar features, diversity and impact of citrulline-reactive autoantibodies.Nature reviews. Rheumatology · 2024Review
- Granzyme serine proteases in inflammation and rheumatic diseases.Nature reviews. Rheumatology · 2024Review
- The Role of Citrullination Modification in CD4Biomolecules · 2024Review
- Granzymes in health and diseases: the good, the bad and the ugly.Frontiers in immunology · 2024Review
- Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis.Nature communications · 2023Article
- Identification of key genes as potential diagnostic and therapeutic targets for comorbidity of myasthenia gravis and COVID-19.Frontiers in neurology · 2023Article
- Proper development of long-lived memory CD4 T cells requires HLA-DO function.Frontiers in immunology · 2023Article
- Stiff person syndrome spectrum disorders; more than meets the eye.Journal of neuroimmunology · 2022Review
- Antibodies against Angiotensin II Type 1 and Endothelin 1 Type A Receptors in Cardiovascular Pathologies.International journal of molecular sciences · 2022Review
- Intersection Between Large Granular Lymphocyte Leukemia and Rheumatoid Arthritis.Frontiers in oncology · 2022Review
- Partnering for the major histocompatibility complex class II and antigenic determinant requires flexibility and chaperons.Current opinion in immunology · 2021Review
- Effect of Peptidylarginine Deiminase 4 on Endothelial Progenitor Cell Function in Peripheral Arterial Disease.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Elevated serum granzyme B levels are associated with disease activity and joint damage in patients with rheumatoid arthritis.The Journal of international medical research · 2020Article
- Citrulline Not a Major Determinant in the Recognition of Peptidylarginine Deiminase 2 and 4 by Autoantibodies in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- Definition of Naturally Processed Peptides Reveals Convergent Presentation of Autoantigenic Topoisomerase I Epitopes in Scleroderma.Arthritis & rheumatology (Hoboken, N.J.) · 2020Observational
- 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
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Authors and funding
12 authors.
Funding
Abstract
Proteolysis of autoantigens can alter normal MHC class II antigen processing and has been implicated in the induction of autoimmune diseases. Many autoantigens are substrates for the protease granzyme B (GrB), but the mechanistic significance of this association is unknown. Peptidylarginine deiminase 4 (PAD4) is a frequent target of autoantibodies in patients with rheumatoid arthritis (RA) and a substrate for GrB. RA is strongly associated with specific MHC class II alleles, and elevated levels of GrB and PAD4 are found in the joints of RA patients, suggesting that GrB may alter the presentation of PAD4 by RA-associated class II alleles. In this study, complementary proteomic and immunologic approaches were utilized to define the effects of GrB cleavage on the structure, processing, and immunogenicity of PAD4. Hydrogen-deuterium exchange and a cell-free MHC class II antigen processing system revealed that proteolysis of PAD4 by GrB induced discrete structural changes in PAD4 that promoted enhanced presentation of several immunogenic peptides capable of stimulating PAD4-specific CD4+ T cells from patients with RA. This work demonstrates the existence of PAD4-specific T cells in patients with RA and supports a mechanistic role for GrB in enhancing the presentation of autoantigenic CD4+ T cell epitopes.
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