Observational studyPloS one2021
Association between inflammatory cytokines and immune-checkpoint molecule in rheumatoid arthritis.
Observational study in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Association between rheumatoid arthritis and pulpal-periapical pathology: a systematic review.Clinical oral investigations · 2023Pooled it
- Risk factors and outcomes for steroid-refractory immune-related hepatotoxicity in locally advanced and metastatic cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Inflammaging-Driven Osteoporosis: Is a Galectin-Targeted Approach Needed?International journal of molecular sciences · 2025Review
- The combination of hydrogels and rutin-loaded black phosphorus nanosheets treats rheumatoid arthritis.Materials today. Bio · 2024Article
- Dual-targeted halofuginone hydrobromide nanocomplexes for promotion of macrophage repolarization and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes in adjuvant-induced arthritis in rats.Journal of pharmaceutical analysis · 2024Article
- Causal relationship, shared genes between rheumatoid arthritis and pulp and periapical disease: evidence from GWAS and transcriptome data.Frontiers in immunology · 2024Article
- Galectin-9 as an indicator of functional limitations and radiographic joint damage in patients with rheumatoid arthritis.Frontiers in immunology · 2024Article
- Article
- Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.Frontiers in immunology · 2023Review
- Increased CEACAM1 expression on peripheral blood neutrophils in patients with rheumatoid arthritis.Frontiers in immunology · 2022Article
- T-cell immunoglobulin and mucin domain 3 is upregulated in rheumatoid arthritis, but insufficient in controlling inflammation.American journal of clinical and experimental 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
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin-9 (Gal-9) mediated ligation of TIM-3 induces the amelioration of autoimmune diseases. TIM-3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune-checkpoint molecules in RA patients.
methodsSerum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble TIM-3 (sTIM-3) and Gal-9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or immune-checkpoint molecules were evaluated between RA patients with low-medium ACPA titers and high ACPA titers.
resultsElevated serum levels of inflammatory cytokines were correlated with DAS28-ESR in RA patients. Although serum levels of sTIM-3 were elevated in RA patients, significant correlations between sTIM-3 and cytokines (IL-6 or TNF-α) were observed exclusively in RA patients with low-medium ACPA titers (<200 U/mL). Serum levels of IL-6 and TNF-α levels were significantly correlated with elevated Gal-9 levels regardless of ACPA status. A significant correlation between IL-6 and Gal-9 was observed in RA patients without advanced joint damage. Conversely, a significant correlation between TNF-α and Gal-9 was observed in RA patients with advanced joint damage.
conclusionsOur data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage.
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