ArticleArthritis research & therapy2016
A specific anti-citrullinated protein antibody profile identifies a group of rheumatoid arthritis patients with a toll-like receptor 4-mediated disease.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Potential Involvement of Platelet-Derived Microparticles and Microparticles Forming Immune Complexes during Monocyte Activation in Patients with Systemic Lupus Erythematosus.Frontiers in immunology · 2018Trial
- Correlation between double-stranded DNA and rheumatoid arthritis.Central-European journal of immunology · 2026Article
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- The Challenges of Local Intra-Articular Therapy.Medicina (Kaunas, Lithuania) · 2024Review
- Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2023Review
- Potential therapeutic targets of macrophages in inhibiting immune damage and fibrotic processes in musculoskeletal diseases.Frontiers in immunology · 2023Review
- Inhibitory Effect of Jinwujiangu Prescription on Peripheral Blood Osteoclasts in Patients with Rheumatoid Arthritis and the Relevant Molecular Mechanism.Mediators of inflammation · 2023Article
- Review
- How Pyroptosis Contributes to Inflammation and Fibroblast-Macrophage Cross-Talk in Rheumatoid Arthritis.Cells · 2022Review
- Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies.International journal of molecular sciences · 2021Article
- Specific TLR4 Blocking Effect of a Novel 3,4-Dihydropyrimidinone Derivative.Frontiers in pharmacology · 2020Article
- Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis.International journal of molecular sciences · 2019Review
- Targeting early changes in the synovial microenvironment: a new class of immunomodulatory therapy?Annals of the rheumatic diseases · 2019Article
- The Inhibitory Role of M2000 (β-D-Mannuronic Acid) on Expression of Toll-like Receptor 2 and 4 in HT29 Cell Line.Recent patents on inflammation & allergy drug discovery · 2019Article
- Proinflammatory Differentiation of Macrophages Through Microparticles That Form Immune Complexes Leads to T- and B-Cell Activation in Systemic Autoimmune Diseases.Frontiers in immunology · 2019Article
- Regulation of Immune Responses and Chronic Inflammation by Fibroblast-Like Synoviocytes.Frontiers in immunology · 2019Review
- Affinity Maturation Drives Epitope Spreading and Generation of Proinflammatory Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- S100 proteins in rheumatic diseases.Nature reviews. Rheumatology · 2018Review
- Association of Distinct Fine Specificities of Anti-Citrullinated Peptide Antibodies With Elevated Immune Responses to Prevotella intermedia in a Subgroup of Patients With Rheumatoid Arthritis and Periodontitis.Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
- Lipopolysaccharide induced vascular smooth muscle cells proliferation: A new potential therapeutic target for proliferative vascular diseases.Cell proliferation · 2017Review
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on their target specificity might provide a simple means to predict therapeutic benefit when neutralizing TLR4 in this disease.
methodsThe capacity of RA synovial fluids (RASF) to stimulate cytokine production in monocytes from patients with RA was analyzed by ELISA. The presence of TLR4 activators in RASF was determined by measuring the levels of ACPA, ACPA subtypes with reactivity to specific citrullinated peptides and other TLR4 ligands. Neutralization of TLR4 signaling was investigated using NI-0101, a therapeutic antibody that targets TLR4.
resultsRASF exhibited a heterogeneous capacity to induce production of proinflammatory cytokines by monocytes isolated from patients with RA. Such cytokine responses were significantly modified by TLR4 blockade achieved using NI-0101. The analysis of the content of RASF and matched sera demonstrated that ACPA fine specificities in patient samples predict cellular response to anti-TLR4 exposure in vitro.
conclusionTLR4 represents a possible therapeutic target in RA. Our study demonstrates that TLR4 inhibition in an ex vivo model of RA pathogenesis can significantly modulate cytokine release and does so in specific subgroups of RA patient-derived samples. It also suggests that ACPA fine profiling has the potential to identify RA patients with a predominantly TLR4-driven pathotype that could be used to predict preferential response to TLR4 antagonism.
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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.