ArticleArthritis and rheumatism2013
Citrullinated calreticulin potentiates rheumatoid arthritis shared epitope signaling.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Characteristics of the (Auto)Reactive T Cells in Rheumatoid Arthritis According to the Immune Epitope Database.International journal of molecular sciences · 2023Review
- The therapeutic mavericks: Potent immunomodulating chaperones capable of treating human diseases.Journal of cellular and molecular medicine · 2023Review
- Endoplasmic Reticulum Stress, Oxidative Stress, and Rheumatic Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- Interplay of Microbiota and Citrullination in the Immunopathogenesis of Rheumatoid Arthritis.Probiotics and antimicrobial proteins · 2022Review
- Characterization and use of the ECV304 autoantigenic citrullinome to understand anti-citrullinated protein/peptide autoantibodies in rheumatoid arthritis.Arthritis research & therapy · 2022Article
- Increased histone citrullination in juvenile idiopathic arthritis.Frontiers in medicine · 2022Article
- HLA-G and the MHC Cusp Theory.Frontiers in immunology · 2022Review
- HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications.Nature reviews. Rheumatology · 2019Review
- Characterization of a Synovial B Cell-Derived Recombinant Monoclonal Antibody Targeting Stromal Calreticulin in the Rheumatoid Joints.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environment interaction in autoimmune arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Synovial cellular and molecular markers in rheumatoid arthritis.Seminars in immunopathology · 2017Review
- The role of autoantibodies in the pathophysiology of rheumatoid arthritis.Seminars in immunopathology · 2017Review
- Epitope Specificity of Anti-Citrullinated Protein Antibodies.Antibodies (Basel, Switzerland) · 2017Review
- Immunogenic HLA-DR-Presented Self-Peptides Identified Directly from Clinical Samples of Synovial Tissue, Synovial Fluid, or Peripheral Blood in Patients with Rheumatoid Arthritis or Lyme Arthritis.Journal of proteome research · 2017Article
- Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis.Journal of immunology research · 2017Review
- Article
- Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid arthritis using LC-MALDI-TOF/TOF.Clinical rheumatology · 2016Article
- Endoplasmic Reticulum Stress Interacts With Inflammation in Human Diseases.Journal of cellular physiology · 2016Review
- Spontaneous destructive periodontitis and skeletal bone damage in transgenic mice carrying a human shared epitope-codingRMD open · 2016Article
- High-level secretion of native recombinant human calreticulin in yeast.Microbial cell factories · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveCitrullinated proteins are immunogenic in rheumatoid arthritis (RA), particularly in patients who carry shared epitope (SE)-coding HLA-DRB1 alleles. The mechanism underlying this association is unknown. We have previously identified the SE as a ligand that interacts with cell surface calreticulin (CRT) and activates immune dysregulation. This study was undertaken to determine the effect of CRT citrullination on SE signaling.
methodsCRT-SE binding affinity was measured by surface plasmon resonance. The role of individual CRT arginine residues was determined by site-directed mutagenesis, and nitric oxide levels were measured using a fluorochrome-based assay. CRT citrullination in synovial tissue samples and cell cultures was determined by 2-dimensional gel electrophoresis, immunoblotting, and mass spectrometry techniques.
resultsSynovial tissue and fibroblast-like synoviocytes from RA patients were found to express a higher abundance of citrullinated CRT than samples from osteoarthritis patients. Citrullinated CRT showed more robust interaction with the SE ligand, and transduced SE signaling at a 10,000-fold higher potency, compared to noncitrullinated CRT. Site-directed mutation analysis identified Arg(205), which is spatially adjacent to the SE binding site in the CRT P-domain, as a dominant inhibitor of SE-CRT interaction and signaling, while a more remote arginine residue, Arg(261), was found to enhance these SE functions.
conclusionOur findings indicate that citrullinated CRT is overabundant in the RA synovium and potentiates SE-activated signaling in vitro. These findings could introduce a new mechanistic model of gene-environment interaction in RA.
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