ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Delineating the role of the HLA-DR4 "shared epitope" in susceptibility versus resistance to develop arthritis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- Murine and Humanized Mouse Models in Autoimmune Disease Research and Therapeutics Development.Biology · 2026Review
- Gut Microbes as the Major Drivers of Rheumatoid Arthritis: Our Microbes Are Our Fortune!Microorganisms · 2025Review
- Review
- Gut microbiota as a sensor of autoimmune response and treatment for rheumatoid arthritis.Immunological reviews · 2024Review
- Thymic mimetic cells: tolerogenic masqueraders.Trends in immunology · 2022Review
- Citrullinated glucose-regulated protein 78 is a candidate target for melanoma immunotherapy.Frontiers in immunology · 2022Article
- Vaccine Can Induce CD4-Mediated Responses to Homocitrullinated PeptidesFrontiers in immunology · 2022Article
- In Vivo Lentiviral Gene Delivery of HLA-DR and Vaccination of Humanized Mice for Improving the Human T and B Cell Immune Reconstitution.Biomedicines · 2021Article
- Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses.Journal for immunotherapy of cancer · 2020Article
- Immunity to Influenza is dependent on MHC II polymorphism: study with 2 HLA transgenic strains.Scientific reports · 2019Article
- Humanized Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Cell-Based Therapies.Frontiers in immunology · 2019Review
- 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 fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis.Science immunology · 2017Article
- Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning.European journal of rheumatology · 2016Article
- Cigarette Smoke Induces Immune Responses to Vimentin in both, Arthritis-Susceptible and -Resistant Humanized Mice.PloS one · 2016Article
- Collagen Specific T-Cell Repertoire and HLA-DR Alleles: Biomarkers of Active Refractory Rheumatoid Arthritis.EBioMedicine · 2015Article
- Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Cytokines pre-determined by genetic factors are involved in pathogenesis of Rheumatoid arthritis.Cytokine · 2015Article
- The gut microbiome in autoimmunity: Sex matters.Clinical immunology (Orlando, Fla.) · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In humans, HLA-DR alleles sharing amino acids at the third hypervariable region with DRB1*0401(shared epitope) are associated with a predisposition to rheumatoid arthritis, whereas DRB1*0402 is not associated with such a predisposition. Both DRB1*0402 and DRB1*0401 occur in linkage with DQ8 (DQB1*0302). We have previously shown that transgenic (Tg) mice expressing HLA-DRB1*0401 develop collagen-induced arthritis. To delineate the role of "shared epitope" and gene complementation between DR and DQ in arthritis, we generated DRB1*0402, DRB1*0401.DQ8, and DRB1*0402.DQ8 Tg mice lacking endogenous class II molecules, AE(o). DRB1*0402 mice are resistant to develop arthritis. In double-Tg mice, the DRB1*0401 gene contributes to the development of collagen-induced arthritis, whereas DRB1*0402 prevents the disease. Humoral response to type II collagen is not defective in resistant mice, although cellular response to type II collagen is lower in *0402 mice compared with *0401 mice. *0402 mice have lower numbers of T cells in thymus compared with *0401 mice, suggesting that the protective effect could be due to deletion of autoreactive T cells. Additionally, DRB1*0402 mice have a higher number of regulatory T cells and show increased activation-induced cell death, which might contribute toward protection. In DRB1*0401.DQ8 mice, activated CD4(+) T cells express class II genes and can present DR4- and DQ8-restricted peptides in vitro, suggesting a role of class II(+) CD4 T cells locally in the joints. The data suggest that polymorphism in DRB1 genes determines predisposition to develop arthritis by shaping the T cell repertoire in thymus and activating autoreactive or regulatory T cells.
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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.