ReviewFrontiers in immunology2022
How RA Associated HLA-DR Molecules Contribute to the Development of Antibodies to Citrullinated Proteins: The Hapten Carrier Model.
Review in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Review
- 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
- Neutrophil extracellular traps in rheumatoid arthritis: biomarkers, drivers, and emerging therapeutic targets.Clinical and experimental immunology · 2026Review
- Gut microbiota and intestinal permeability in rheumatoid arthritis: pathogenic mechanisms.Frontiers in immunology · 2026Review
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- The interactions between HLA alleles and immune indicators were associated with the risk of rheumatoid arthritis.Clinical rheumatology · 2025Article
- Genomic information contributing to the understanding of rheumatic diseases.EULAR rheumatology open · 2025Article
- Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases.Journal of translational autoimmunity · 2025Review
- Animal Models in Rheumatoid Arthritis: Is There a Correlation Between Autoantibodies in Human Pathology and Animal Models?Biology · 2025Review
- Article
- Citrullinated peptides of peptidyl arginine deiminase 4 as major B-cell epitopes in patients with rheumatoid arthritis.Frontiers in immunology · 2025Article
- Infectious and Commensal Bacteria in Rheumatoid Arthritis-Role in the Outset and Progression of the Disease.International journal of molecular sciences · 2024Review
- How underappreciated autoinflammatory (innate immunity) mechanisms dominate disparate autoimmune disorders.Frontiers in immunology · 2024Review
- Effect of the immune cells and plasma metabolites on rheumatoid arthritis: a mediated mendelian randomization study.Frontiers in endocrinology · 2024Article
- A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss.Frontiers in immunology · 2023Article
- Editorial: Targeting antigen processing and presentation in autoimmune and autoinflammatory disorders.Frontiers in immunology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The risk to develop ACPA positive rheumatoid arthritis (RA), the most destructive type of autoimmune arthritis, is carried by HLA-DRB1 alleles containing a 5 amino acid motif: the shared epitope (SE). RA is preceded by the emergence of disease specific anti citrullinated protein antibodies (ACPA). SE positive HLA-DRB1 alleles are associated with ACPA and ACPA positive RA, not with ACPA negative RA, suggesting that ACPA contribute to the pathogenesis of RA. Understanding how HLA-DRB1 genotypes influence ACPA could lead to a curative or preventive treatment of RA. The "Shared epitope binds citrullinated peptides " hypothesis suggests that RA associated HLA-DR alleles present citrullinated peptides to T cells that help ACPA producing B cells. The "Hapten carrier model" suggests that PAD4 is the target of the T cells which help ACPA specific B cells through a hapten carrier mechanism in which PAD4 is the carrier and citrullinated peptides are the haptens. Direct binding assay of citrullinated peptides to purified HLA-DR molecules does not support the "shared epitope binds citrullinated peptides" hypothesis. The Odds Ratios to develop ACPA positive RA associated with each of 12 common HLA-DRB1 genotypes match the probability that the two HLA-DR molecules they encode can bind at least one peptide from PAD4, not from citrullinated fibrinogen. Thus, PAD4 tolerization might stop the carrier effect and switch off production of ACPA.
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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.