ArticleAnnals of the rheumatic diseases2019
Targeting early changes in the synovial microenvironment: a new class of immunomodulatory therapy?
Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Crosstalk between macrophages and fibroblasts contributes to inflammation and damage in giant cell arteritis.Rheumatology (Oxford, England) · 2026Article
- Platinum-doped emodin carbon dots mitigate sepsis-induced lung injury by targeting the gut-lung axis.Journal of nanobiotechnology · 2025Article
- Synovial matrix turnover controls immune cell spatial patterning in inflammation resolution.Molecular systems biology · 2025Article
- Selective agonists of KIR and NKG2A to evade missing self response of natural killer cells.Scientific reports · 2025Article
- Small moleculeActa pharmaceutica Sinica. B · 2024Article
- Extracellular matrix complexity in biomarker studies: a novel assay detecting total serum tenascin-C reveals different distribution to isoform-specific assays.Frontiers in immunology · 2023Article
- Tenascin-C in fibrosis in multiple organs: Translational implications.Seminars in cell & developmental biology · 2022Review
- Immunological memory in rheumatic inflammation - a roadblock to tolerance induction.Nature reviews. Rheumatology · 2021Review
- Location, location, location: how the tissue microenvironment affects inflammation in RA.Nature reviews. Rheumatology · 2021Review
- Laser treatment of synovial inflammatory process in experimentally induced microcrystalline arthritis in Wistar rats.Lasers in medical science · 2021Article
- YAP/TAZ: Key Players for Rheumatoid Arthritis Severity by Driving Fibroblast Like Synoviocytes Phenotype and Fibro-Inflammatory Response.Frontiers in immunology · 2021Article
- Macrophages and Extracellular Matrix in Breast Cancer: Partners in Crime or Protective Allies?Frontiers in oncology · 2021Review
- Matrix-Targeting Immunotherapy Controls Tumor Growth and Spread by Switching Macrophage Phenotype.Cancer immunology research · 2020Article
- Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment.Frontiers in immunology · 2020Review
- Tenascin-C in Osteoarthritis and Rheumatoid Arthritis.Frontiers in immunology · 2020Review
- Extracellular matrix in the crosshairs.Nature reviews. Rheumatology · 2019Article
- Airway Epithelial Cells Generate Pro-inflammatory Tenascin-C and Small Extracellular Vesicles in Response to TLR3 Stimuli and Rhinovirus Infection.Frontiers in immunology · 2019Article
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
objectivesControlled immune responses rely on integrated crosstalk between cells and their microenvironment. We investigated whether targeting proinflammatory signals from the extracellular matrix that persist during pathological inflammation provides a viable strategy to treat rheumatoid arthritis (RA).
methodsMonoclonal antibodies recognising the fibrinogen-like globe (FBG) of tenascin-C were generated by phage display. Clones that neutralised FBG activation of toll-like receptor 4 (TLR4), without impacting pathogenic TLR4 activation, were epitope mapped by crystallography. Antibodies stained synovial biopsies of patients at different stages of RA development. Antibody efficacy in preventing RA synovial cell cytokine release, and in modulating collagen-induced arthritis in rats, was assessed.
resultsTenascin-C is expressed early in the development of RA, even before disease diagnosis, with higher levels in the joints of people with synovitis who eventually developed RA than in people whose synovitis spontaneously resolved. Anti-FBG antibodies inhibited cytokine release by RA synovial cells and prevented disease progression and tissue destruction during collagen-induced arthritis.
conclusionsEarly changes in the synovial microenvironment contribute to RA progression; blocking proinflammatory signals from the matrix can ameliorate experimental arthritis. These data highlight a new drug class that could offer early, disease-specific immune modulation in RA, without engendering global immune suppression.
Indexed as
Identifiers
What OpenQuestion holds
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.