High Interleukin-37 (IL-37) Expression and Increased Mucin-Domain Containing-3 (TIM-3) on Peripheral T Cells in Patients with Rheumatoid Arthritis

Song, Lijun; Wang, Yunqing; Sui, Yameng; Sun, Jiao; Dong, Li; Li, Guosheng; Liu, Jianwei; Li, Tianwang; Shu, Qiang

doi:10.12659/msm.909254

Cited by 19 publications

(11 citation statements)

References 51 publications

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“…Elevated expression of IL‐37 was positively correlated with disease activity index. These findings are in agreement with previous studies . In recent years, increasing evidence has shown that IL‐37 is implicated in rheumatic autoimmune diseases.…”

Section: Discussionsupporting

confidence: 93%

Elevated expression of interleukin‐37 in patients with rheumatoid arthritis

et al. 2019

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Aim This study aims to discuss plasma and messenger RNA (mRNA) levels of interleukin (IL)‐37 in rheumatoid arthritis (RA) patients and evaluate the potential of plasma IL‐37 as a biomarker for RA. Method Plasma IL‐37 levels and IL‐37 mRNA relative concentrations were measured by enzyme‐linked immunosorbent assay (ELISA) and quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). We discussed the association of IL‐37 levels and clinical, laboratory parameters in RA patients in a training cohort. Plasma IL‐37 levels were tested for discriminatory capacity by receiver operating characteristic (ROC) curve analysis. We then validated plasma IL‐37 expression in a cohort of 598 patients (230 RA, 107 systemic lupus erythematosus [SLE], 100 osteoarthritis [OA], 62 gout, 51 primary Sjögren's syndrome [pSS], 48 ankylosing spondylitis [AS]). Results Both plasma levels of IL‐37 and mRNA levels of IL‐37 were elevated in RA patients compared to those in healthy controls in the training cohort, and there was a good diagnostic ability to predict RA (area under the curve [AUC] = 0.97). Plasma IL‐37 levels were significantly related to Disease Activity Score of 28 joints ‐ erythrocyte sedimentation rate (DAS28‐ESR) (rs = 0.459, P < 0.001). The levels of IL‐37 mRNA were related to plasma IL‐37 levels (rs = 0.642, P < 0.001), DAS28‐ESR (r = 0.641, P < 0.001) and C‐reactive protein (rs = 0.603, P < 0.001). In the validation cohort, when plasma IL‐37 in RA patients compared with that in SLE, OA, gout, pSS and AS patients, the AUC was 0.86, 0.87, 0.91, 0.87, 0.92, respectively. Conclusion IL‐37 expression was increased in RA patients, and correlated with disease activity. IL‐37 may be a biomarker for the diagnosis of RA.

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Section: Discussionsupporting

confidence: 93%

Elevated expression of interleukin‐37 in patients with rheumatoid arthritis

et al. 2019

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“…In our previous report, serum Gal–9 and sTIM–3 were significantly elevated in RA patients compared with healthy subjects [ 21 , 22 ]. A relationship between proinflammatory cytokines and Gal–9/TIM–3 has been reported in RA patients [ 23 , 24 ], so we hypothesized that immune–checkpoint molecules are possible modulators of immunopathology in RA through their interactions with cytokines. In this study we investigated the influence of these combined biomarkers, including autoantibodies, cytokines, and immune-checkpoint molecules, on the disease activity of RA.…”

Section: Introductionmentioning

confidence: 99%

Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis

et al. 2021

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Background Anti-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. Methods Serum 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. Results Elevated 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. Conclusions Our 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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“…After that, the publications continued to rise in IL-37 research, which implies that IL-37 has also gained much attention. Increased levels of circulating IL-37 have been reported in the patients with rheumatoid arthritis (37,(44)(45)(46)(47)(48), multiple sclerosis (49)(50)(51), and systemic lupus erythematosus (12,(52)(53)(54). Patients with rheumatoid arthritis demonstrated an increased level of synovial IL-1R8, which is essential for the antiinflammatory effects of IL-37.…”

Section: Discussionmentioning

confidence: 99%

The intellectual base and research fronts of IL-37: A bibliometric review of the literature from WoSCC

et al. 2022

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BackgroundIL-37 is a recently identified cytokine with potent immunosuppressive functions. The research fronts of IL-37 are worth investigating, and there is no bibliometric analysis in this field. The purpose of this study is to construct the intellectual base and predict research hotspots of IL-37 research both quantitatively and qualitatively according to bibliometric analysis.MethodsThe articles were downloaded from the Web of Science Core Collection (WoSCC) database from the inception of the database to 1 April 2022. CiteSpace 5.8.R3 (64-bit, Drexel University, Philadelphia, PA, USA) and Online Analysis Platform of Literature Metrology (https://bibliometric.com/) were used to perform bibliometric and knowledge-map analyses.ResultsA total of 534 papers were included in 200 academic journals by 2,783 authors in 279 institutions from 50 countries/regions. The journal Cytokine published the most papers on IL-37, while Nature Immunology was the most co-cited journal. The publications belonged mainly to two categories of Immunology and Cell Biology. USA and China were the most productive countries. Meanwhile, the University of Colorado Denver in USA produced the highest number of publications followed by Radboud University Nijmegen in the Netherlands and Monash University in Australia. Charles A. Dinarello published the most papers, while Marcel F. Nold had the most co-citations. Top 10 co-citations on reviews, mechanisms, and diseases were regarded as the knowledge base. The keyword co-occurrence and co-citations of references revealed that the mechanisms and immune-related disorders were the main aspects of IL-37 research. Notably, the involvement of IL-37 in various disorders and the additional immunomodulatory mechanisms were two emerging hotspots in IL-37 research.ConclusionsThe research on IL-37 was thoroughly reviewed using bibliometrics and knowledge-map analyses. The present study is a benefit for academics to master the dynamic evolution of IL-37 and point out the direction for future research.

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High Interleukin-37 (IL-37) Expression and Increased Mucin-Domain Containing-3 (TIM-3) on Peripheral T Cells in Patients with Rheumatoid Arthritis

Cited by 19 publications

References 51 publications

Elevated expression of interleukin‐37 in patients with rheumatoid arthritis

Elevated expression of interleukin‐37 in patients with rheumatoid arthritis

Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis

The intellectual base and research fronts of IL-37: A bibliometric review of the literature from WoSCC

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