ArticleThe Journal of experimental medicine2013
A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 226 papers.
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Who cites it
226 citing papers in PubMed, 407 citations in OpenAlex.
- Randomized phase I trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis.JCI insight · 2022Trial
- HLA-DRB1 risk alleles for RA are associated with differential clinical responsiveness to abatacept and adalimumab: data from a head-to-head, randomized, single-blind study in autoantibody-positive early RA.Arthritis research & therapy · 2021Trial
- Interleukin-6 (IL-6) Receptor Antagonist Protects Against Rheumatoid Arthritis.Medical science monitor : international medical journal of experimental and clinical research · 2016Trial
- Article
- Vaccines for Autoimmune Diseases: Stopping Triggers, Restoring BalanceA Systematic Review with Qualitative Synthesis.Mediterranean journal of rheumatology · 2026Review
- Autoantibodies and T Cells Target Citrullinated and Homocitrullinated Antigens in Rheumatoid Arthritis.Immunological reviews · 2026Review
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Decoding the association between microorganisms and autoimmunity: a multifaceted review of evidence on specific pathogens that trigger autoimmune diseases.Clinical and experimental medicine · 2026Review
- A Comprehensive HLA-DR4 MHC Class II Tetramer Platform for the Detection and Functional Validation of Post-Translational Modification Neoantigens.International journal of molecular sciences · 2026Article
- Coxsackievirus B escapes antiviral CD8Science advances · 2026Article
- Review
- 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
- Distinct HLA Associations for Antibody Multireactivity With Citrulline-Containing Type II Collagen Epitopes Versus More Limited Antibody Reactivity With Citrulline-Containing IgG Epitopes in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Autophagy in Rheumatoid Arthritis: Molecular Mechanisms, Diagnostic Biomarkers, and Emerging Therapeutic Strategies.Inflammation · 2026Review
- MHC II MAPPs for High-Confident Immunogenicity Risk Assessment of Biotherapeutics.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis.Frontiers in immunology · 2026Article
- HLA class I-naturally presented synovial tissue peptides are recognized by CD8+ T lymphocytes from rheumatoid arthritis patients.Frontiers in immunology · 2026Article
- Phytochemicals and nanoformulation strategies for rheumatoid arthritis: mechanistic insights, therapeutic advances, and translational challenges.Inflammopharmacology · 2026Review
- Distribution of HLA-ABC allele groups in a cohort of Chilean rheumatoid arthritis patients and healthy individuals.Biological research · 2025Article
166 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen (HLA)-DRB1 locus that possesses the shared susceptibility epitope (SE) and the citrullination of self-antigens. We show how citrullinated aggrecan and vimentin epitopes bind to HLA-DRB1*04:01/04. Citrulline was accommodated within the electropositive P4 pocket of HLA-DRB1*04:01/04, whereas the electronegative P4 pocket of the RA-resistant HLA-DRB1*04:02 allomorph interacted with arginine or citrulline-containing epitopes. Peptide elution studies revealed P4 arginine-containing peptides from HLA-DRB1*04:02, but not from HLA-DRB1*04:01/04. Citrullination altered protease susceptibility of vimentin, thereby generating self-epitopes that are presented to T cells in HLA-DRB1*04:01(+) individuals. Using HLA-II tetramers, we observed citrullinated vimentin- and aggrecan-specific CD4(+) T cells in the peripheral blood of HLA-DRB1*04:01(+) RA-affected and healthy individuals. In RA patients, autoreactive T cell numbers correlated with disease activity and were deficient in regulatory T cells relative to healthy individuals. These findings reshape our understanding of the association between citrullination, the HLA-DRB1 locus, and T cell autoreactivity in RA.
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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.