T cells, natural killer cells, and γδT cells in a large patient cohort with rheumatoid arthritis: influence of age and anti-rheumatic therapy

Ec, Schwaneck; Renner, Regina; Junker, L.; Hp, Tony; Kleinert, Stefan; Gernert, Michael; Schmalzing, Marc; Gadeholt, Ottar

doi:10.1080/03009742.2019.1634755

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…Previous studies suggested that mast cells were aberrantly regulated in RA synovium and were mainly activated by TLRs (toll-like receptors), PAMP (pathogen-associated molecular patterns), and FcγR (Fc gamma receptor) ( 28 , 29 ). Moreover, dendritic cells, NK cells, and regulatory T cells were demonstrated to play a significant role in the development of RA ( 30 , 31 ). Therefore, the present results are consistent with previous reports and highlights the importance of these cells in the pathogenesis of RA by bioinformatic analysis.…”

Section: Discussionmentioning

confidence: 99%

Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis

2021

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BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by inflammatory cell infiltration, leading to persistent synovitis and joint destruction. The pathogenesis of RA remains unclear. This study aims to explore the immune molecular mechanism of RA through bioinformatics analysis.MethodsFive microarray datasets and a high throughput sequencing dataset were downloaded. CIBERSORT algorithm was performed to evaluate immune cell infiltration in synovial tissues between RA and healthy control (HC). Wilcoxon test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the significantly different infiltrates of immune cells. Differentially expressed genes (DEGs) were screened by “Batch correction” and “RobustRankAggreg” methods. Functional correlation of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Candidate biomarkers were identified by cytoHubba of Cytoscape, and their diagnostic effectiveness was predicted by Receiver Operator Characteristic Curve (ROC) analysis. The association of the identified biomarkers with infiltrating immune cells was explored using Spearman’s rank correlation analysis in R software.ResultsTen significantly different types of immune cells between RA and HC were identified. A total of 202 DEGs were obtained by intersection of DEGs screened by two methods. The function of DEGs were significantly associated with immune cells. Five hub genes (CXCR4, CCL5, CD8A, CD247, and GZMA) were screened by R package “UpSet”. CCL5+CXCR4 and GZMA+CD8A were verified to have the capability to diagnose RA and early RA with the most excellent specificity and sensitivity, respectively. The correlation between immune cells and biomarkers showed that CCL5 was positively correlated with M1 macrophages, CXCR4 was positively correlated with memory activated CD4+ T cells and follicular helper T (Tfh) cells, and GZMA was positively correlated with Tfh cells.ConclusionsCCL5, CXCR4, GZMA, and CD8A can be used as diagnostic biomarker for RA. GZMA-Tfh cells, CCL5-M1 macrophages, and CXCR4- memory activated CD4+ T cells/Tfh cells may participate in the occurrence and development of RA, especially GZMA-Tfh cells for the early pathogenesis of RA.

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Section: Discussionmentioning

confidence: 99%

Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis

2021

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“…Our study observed that in RA patients with high levels of Th2, Th17, and Th17/Treg on the basis of the original treatment, exogenous TCZ and low dose of IL-2 can rapidly and safely reduce the DAS28 score and alleviate the disease in a short period, effectively promote the moderate proliferation of Tregs and reduce the level of Th cells, which is consistent with the previous results of TCZ combined with other DMARDs ( 42 ). Meanwhile, more female patients were recruited in this study, but relevant literature showed that gender did not affect the distribution ratio of peripheral blood immune cells and the therapeutic effect of tocilizumab, so it was believed that gender did not affect the judgment of results in this study ( 43 ).…”

Section: Discussionmentioning

confidence: 97%

The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis

Zhang,

Chen,

Wang

et al. 2024

Front. Immunol.

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BackgroundImmunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients.MethodsFifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment.ResultsCompared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients.ConclusionExogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration.Clinical trial registrationhttps://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.

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“…Schwaneck et al. documented rising numbers of NK (CD56 + , CD3 − , CD14 − ) cells with age in RA patients in the peripheral blood and those with current TNF-inhibition therapy ( 40 ), which demonstrated the complex factors influencing the status of NK cells. Interestingly, we observed a moderate negative correlation of NK cells in peripheral blood with arthritis index score, which agreed with Lin et al., who showed that RA disease activity (DAS28) exhibited an inverse correlation with the percentages of CD56 + CD3 − NK cells ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Cells Infiltration in the Joints Exacerbates Collagen-Induced Arthritis

Wang

Zhou

et al. 2022

Front. Immunol.

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IntroductionThe role of natural killer (NK) cells in rheumatoid arthritis remains controversial. We aimed to assess the role of NK cells in the pathogenesis of rheumatoid arthritis.Materials and MethodsThe percentage of NK cells in the peripheral blood, spleen, lymph nodes and inflamed paws from collagen-induced arthritis mice were examined through the disease progression. Correlation between the proportion of NK cells and subsets with arthritis score, histopathological changes, and bone destruction were evaluated. Adoptive cell transfer was performed to determine the effect of NKp46+NK cells on arthritis development, and the role of receptor NKp46 was explored with NKp46 knockout mice.ResultsThe percentage of NK cells in peripheral blood decreased at the late stage of the disease and negatively correlated with arthritis score. NK cells increased in the inflamed paws during arthritis development and were positively associated with arthritis score, histopathological change, and bone destruction. Adoptive transfer of NKp46+NK cells before disease onset resulted in increased NK cells infiltration in the joints, higher incidence of arthritis, more severe clinical symptoms, and more pronounced joint inflammation and bone damage. NKp46 deficiency had no significant influence on the incidence and severity of arthritis in collagen-induced arthritis mice.ConclusionsNK cell infiltration in the joints positively correlates with arthritis progression, inflammation, and bone destruction. The pathogenic role of NK cells in rheumatoid arthritis may be independent of the receptor NKp46.

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T cells, natural killer cells, and γδT cells in a large patient cohort with rheumatoid arthritis: influence of age and anti-rheumatic therapy

Cited by 7 publications

References 11 publications

Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis

Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis

The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis

Natural Killer Cells Infiltration in the Joints Exacerbates Collagen-Induced Arthritis

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