ArticleJournal of immunology (Baltimore, Md. : 1950)2013
An HLA-DRB1-coded signal transduction ligand facilitates inflammatory arthritis: a new mechanism of autoimmunity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 31 citations in OpenAlex.
- Shared Epitope-PositiveNeurology(R) neuroimmunology & neuroinflammation · 2026Article
- Identification and Screening of Lactate-Related Genes as Molecular Markers for Early Diagnosis of Steroid-Induced Osteonecrosis of the Femoral Head.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Identification of epistatic SNP combinations in rheumatoid arthritis using LAMPLINK and Japanese cohorts.Journal of human genetics · 2024Article
- Indigenous Nigeria medicinal herbal remedies: A potential source for therapeutic against rheumatoid arthritis.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Endoplasmic Reticulum Stress, Oxidative Stress, and Rheumatic Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- HLA-G and the MHC Cusp Theory.Frontiers in immunology · 2022Review
- Current research status of HLA in immune-related diseases.Immunity, inflammation and disease · 2021Review
- HLA-DRB1 allelic epitopes that associate with autoimmune disease risk or protection activate reciprocal macrophage polarization.Scientific reports · 2021Article
- Uncovering a Shared Epitope-Activated Protein Citrullination Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications.Nature reviews. Rheumatology · 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
- Human Leukocyte Antigen-Disease Associations in Rheumatoid Arthritis.Rheumatic diseases clinics of North America · 2017Review
- HLA-DRB1 the notorious gene in the mosaic of autoimmunity.Immunologic research · 2017Article
- A reciprocal HLA-Disease Association in Rheumatoid Arthritis and Pemphigus Vulgaris.Frontiers in bioscience (Landmark edition) · 2017Review
- Basement membranes and autoimmune diseases.Matrix biology : journal of the International Society for Matrix Biology · 2017Review
- Spontaneous destructive periodontitis and skeletal bone damage in transgenic mice carrying a human shared epitope-codingRMD open · 2016Article
- Shared epitope-antagonistic ligands: a new therapeutic strategy in mice with erosive arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- The quest for better understanding of HLA-disease association: scenes from a road less travelled by.Discovery medicine · 2013Review
- A small shared epitope-mimetic compound potently accelerates osteoclast-mediated bone damage in autoimmune arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Gender-biased regulation of human IL-17-producing cellsJournal of immune based therapies, vaccines and antimicrobials · 2013Article
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10 authors at 1 institution in 1 country.
Funding
Abstract
Particular alleles of HLA contribute to disease susceptibility and severity in many autoimmune conditions, but the mechanisms underlying these associations are often unknown. In this study, we demonstrate that the shared epitope (SE), an HLA-DRB1-coded sequence motif that is the single most significant genetic risk factor for erosive rheumatoid arthritis, acts as a signal transduction ligand that potently activates osteoclastogenesis, both in vitro and in vivo. The SE enhanced the production of several pro-osteoclastogenic factors and facilitated osteoclast (OC) differentiation in mouse and human cells in vitro. Transgenic mice expressing a human HLA-DRB1 allele that code the SE motif demonstrated markedly higher propensity for osteoclastogenesis and enhanced bone degradation capacity ex vivo. In addition, the SE enhanced the differentiation of Th17 cells expressing the receptor activator for NF-κB ligand. When the two agents were combined, IL-17 and the SE enhanced OC differentiation synergistically. When administered in vivo to mice with collagen-induced arthritis, the SE ligand significantly increased arthritis severity, synovial tissue OC abundance, and bone erosion. Thus, the SE contributes to arthritis severity by activating an OC-mediated bone-destructive pathway. These findings suggest that besides determining the target specificity of autoimmune responses, HLA molecules may influence disease outcomes by shaping the pathogenic consequences of such responses.
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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.