Combined Treatment of Etanercept and MTX Reverses Th1/Th2, Th17/Treg Imbalance in Patients with Rheumatoid Arthritis

Chen, Lina; Wang, Conghua; Li, Nan; Zhu, Ping

doi:10.1007/s10875-011-9542-6

Cited by 138 publications

(115 citation statements)

References 29 publications

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“…16 In RA patients treated with MTX alone or in combination with etanercept, no significant changes were observed in serum concentration of IL-4 and IL-10. 43 In our study, itolizumab did not have a clear effect on IL-10, as was previously demonstrated in psoriasis patients receiving the antibody as monotherapy. 35 Regarding IL-4, its levels were higher in the group receiving the antibody, and this effect was maintained during the follow up.…”

Section: Discussionsupporting

confidence: 80%

“…16 In RA patients treated with MTX, a significant decrease in IL-6, IFN-g 54 and TNF 54,55 levels has also been seen. The same effect was obtained in the cases of IL-6 and TNF in patients treated with a combination of MTX with either etanercept 43 or abatacept. 56 In the first study, IFN-g levels did not change, 43 while the second combination was able to diminish synovial inflammatory gene expression, including IFN-g. 57 In the present study, we used a mAb targeting CD6, which is expressed mainly on T cells and is related with differentiation, survival and activation of these lymphocytes.…”

Section: Discussionsupporting

confidence: 71%

“…The same effect was obtained in the cases of IL-6 and TNF in patients treated with a combination of MTX with either etanercept 43 or abatacept. 56 In the first study, IFN-g levels did not change, 43 while the second combination was able to diminish synovial inflammatory gene expression, including IFN-g. 57 In the present study, we used a mAb targeting CD6, which is expressed mainly on T cells and is related with differentiation, survival and activation of these lymphocytes. 20,21 A significant decrease in the levels of the proinflammatory cytokines IL-6, TNF and IFN-g was found in patients treated with anti-CD6 itolizumab in combination with MTX even when measured 12 weeks after treatment ended.…”

Section: Discussionsupporting

confidence: 71%

“…42 As the majority of the biological drugs approved for RA treatment focus on inflammatory cytokines, changes in the immune cell profile are insufficiently studied when these drugs are combined with MTX. In one study 43 in which RA patients were treated during 12 weeks with MTX plus etanercept, a TNF inhibitor comprising the TNF receptor fused to the Fc portion of human IgG1, 44 a decrease in Th1 and Th17 cells was observed. 43 In another study 45 evaluating the effect of abatacept, a T cell activation-blocker consisting of the extracellular domain of CTLA-4 fused to the Fc portion of human IgG1, 46 a significant decrease in IL-17-and IFN-g-producing CD8+ T cells was observed after 6 months of treatment, while after 12 months IL-17-producing CD4+ T cells also decreased.…”

Section: Discussionmentioning

confidence: 99%

“…In one study 43 in which RA patients were treated during 12 weeks with MTX plus etanercept, a TNF inhibitor comprising the TNF receptor fused to the Fc portion of human IgG1, 44 a decrease in Th1 and Th17 cells was observed. 43 In another study 45 evaluating the effect of abatacept, a T cell activation-blocker consisting of the extracellular domain of CTLA-4 fused to the Fc portion of human IgG1, 46 a significant decrease in IL-17-and IFN-g-producing CD8+ T cells was observed after 6 months of treatment, while after 12 months IL-17-producing CD4+ T cells also decreased. 45 In our study, in those patients treated only with MTX, ALC remained stable during the whole study.…”

Section: Discussionmentioning

confidence: 99%

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Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Aira

Hernández

Prada³

et al. 2015

mAbs

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(2016) Immunological evaluation of rheumatoid arthritis patients treated with itolizumab, mAbs, 8:1, 187-195, DOI: 10.1080/19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Aira

Hernández

Prada³

et al. 2015

mAbs

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Citrulline‐Specific Th1 Cells Are Increased in Rheumatoid Arthritis and Their Frequency Is Influenced by Disease Duration and Therapy

James

Rieck

Pieper

et al. 2014

Arthritis & Rheumatology

183

202

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Objective Rheumatoid arthritis is thought to be a T cell mediated disease, based on its strong association with HLA class II alleles, clinical responsiveness to T cell directed therapies and the presence of CD4 T cells in rheumatoid joints. The presence of ACPA in RA serum and the association of these antibodies with HLA-DR4 alleles implicates citrullinated specific autoreactive T cells in the development and progression of RA. The goal of this study was to determine the character and specificity of auto-reactive T cell responses in RA. Methods We developed a panel of HLA-DRB1*04:01 tetramers, selecting citrullinated peptides from synovial antigens and verifying their immunogenicity in DRB1*04:01 transgenic mice. Seven tetramers were used to examine the ex vivo frequency and surface phenotype of cit-specific T cells in RA and healthy subjects with DRB1*04:01 haplotypes using a magnetic enrichment procedure. Results Cit-specific T cells were detectable in peripheral blood samples from both healthy subjects and RA patients. In comparison to healthy subjects, RA patients had significantly higher frequencies of cit-specific T cells and a greater proportion of these cells displayed a Th1 memory phenotype. Among RA subjects the frequency of cit-specific T cells was highest within the first 5 years after diagnosis of RA and was decreased in patients taking biologic therapies irrespective of disease duration. Conclusion These findings link the presence of ACPA in RA with Th1 cells specific to citrullinated epitopes and provide tools for disease-specific immunomonitoring of autoreactive T cells.

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Gallic acid regulates immune response in a mouse model of rheumatoid arthritis

Liu

Feng

2023

Immunity Inflam & Disease

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Introduction Previous studies revealed that gallic acid (GA) exerts anti‐inflammation and immuno‐regulatory properties. This study aims to explore the pharmacological activities of GA in collagen‐induced arthritis (CIA) mouse model. Methods Male DBA/1J mice were used to construct the CIA model. The mice were administrated with GA for 3 weeks. Clinical arthritis scores and hind paw volume were evaluated over the experimental period. qPCR and Western blot analysis were used to determine the levels of matrix metallopeptidases (MMPs) and cytokines. In addition, flow cytometry was used to measure the populations of Th17 and Treg cells. ELISAs were used to determine the cytokines in the serum and ankle joint tissues. Results Treatment of GA (40 and 80 mg/kg/d) reduced clinical arthritis scores and hind paw volume in the CIA mouse model. Besides, treatment of GA reduced the overexpression of MMPs and modulated the dysregulation of inflammation‐related cytokines. Flow cytometry showed that treatment of GA decreased the population of Th17 cells, and increased the population of Treg cells, as supported by treatment of GA regulated the Th17/Treg‐related cytokines. Conclusions GA attenuates symptoms in the CIA mouse model by anti‐inflammation and regulating Th17/Treg cell imbalance.

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Combined Treatment of Etanercept and MTX Reverses Th1/Th2, Th17/Treg Imbalance in Patients with Rheumatoid Arthritis

Abstract: Etanercept in combination with MTX ameliorates RA activity by normalizing the distribution of Th17 and Treg, and their related cytokines, which may partly explain the mechanism of combined therapy of Etanercept plus MTX in RA treatment.

Cited by 138 publications

References 29 publications

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Citrulline‐Specific Th1 Cells Are Increased in Rheumatoid Arthritis and Their Frequency Is Influenced by Disease Duration and Therapy

Gallic acid regulates immune response in a mouse model of rheumatoid arthritis

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