Alterations in Cytokine Profile and Dendritic Cells Subsets in Peripheral Blood of Rheumatoid Arthritis Patients before and after Biologic Therapy

Marti, Luciana Cavalheiro; Golmia, Ricardo Prado; Golmia, Andrea Pimentel Fonseca; Paes, Ângela Tavares; Guilhen, Daiane Donna; Moreira-Filho, Carlos Alberto; Scheinberg, Morton

doi:10.1111/j.1749-6632.2009.04740.x

Cited by 26 publications

(16 citation statements)

References 35 publications

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“…Consistently with us, a deficit in serum Th1 cytokines in active RA and/or their negative relationship with disease activity have also been reported [34, 35, 41, 42, 53]. It is worthy of note, however, that our results contradict several previous reports showing increased or unchanged circulating Th1 cytokines in RA [12, 32, 33, 35] only in the part considering patients with the most advanced disease. Furthermore, in the same group of patients, we did not observe any influence of long-term iTNF treatment on changes in PB Th1 cell responses, as they entered the study with compromised baseline Th1 cytokine values.…”

Section: Discussionsupporting

confidence: 91%

Patients with the most advanced rheumatoid arthritis remain with Th1 systemic defects after TNF inhibitors treatment despite clinical improvement

et al. 2013

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Systemic immune defects might reflect severely dysregulated control of chronic inflammation related to disease progression. Th17/Treg cell imbalance has been demonstrated to be involved in rheumatoid arthritis (RA) pathogenesis. Despite controversial results, a growing anti-inflammatory role in this process has been recently attributed to Th1 responses. The aim of the study was to estimate the extent of Th1/Th17/Treg imbalance in peripheral blood (PB) of patients with short- and long-term RA in relation to cytokine milieu and its reversal after therapy with methotrexate and/or TNF inhibitors, respectively. Patients with different duration of RA (median 6 vs. 120 months) in the active phase of RA were enrolled in this study. We performed flow cytometric analysis of PB Th1, Th17, and Treg populations together with estimation of serum cytokine concentrations using cytometric bead array. Disease activity was calculated on the basis of clinical and biochemical indices of inflammation (DAS28, ESR, CRP). All parameters were measured and correlated with each other before and after 6 months therapy. Elevated levels of circulating Th17 cells and IL-6 were found in all active patients, of which Th17 cells were down-regulated by the treatment. Significantly reduced Th1 and functional CTLA-4+ Treg cell frequencies as well as Th1 cytokines observed only in progressive RA seemed to be irreversible. Although therapy induced clinical improvement in almost all patients, those with advanced RA remained with signs of inflammation. Our report demonstrates that both the extent of systemic immune abnormalities and their restoration are dependent on duration of the active RA.

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Section: Discussionsupporting

confidence: 91%

Patients with the most advanced rheumatoid arthritis remain with Th1 systemic defects after TNF inhibitors treatment despite clinical improvement

et al. 2013

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“…Так, L. Marti и соавт. [35] выявили снижение уровня ИФНγ с 16,2±5,9 до 9,1±3,8 пг/мл (р<0,05), в то время как уровень ИЛ6 значительно не из-менялся. M. Umemura и соавт.…”

Section: Discussionunclassified

The Effect of Abatacept on Blood Biomarkers in Patients With Rheumatoid Arthritis

Борисова¹,

Lukina²,

Сигидин³

et al. 2017

Naučno-praktičeskaâ revmatologiâ

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Objective: to estimate changes in the cytokine profile in patients receiving abatacept (ABC).Subjects and methods. The investigation enrolled 44 patients with rheumatoid arthritis (RA) who had been unsuccessfully treated with disease-modifying antirheumatic drugs and biological agents. A control group included 16 healthy donors. The majority of patients were women who were positive for rheumatoid factor (RF) (80%) and antibodies to cyclic citrullinated peptide (ACCP) (79.5%); the mean age was 49.6±13.9 years; the median disease duration was 2 [1.4; 3] years with high RA activity (mean DAS28, 5.2±0.8). The serum concentrations of interleukin (IL) 1β, IL-6, IL-17AF, tumor necrosis factor-α (TNF-α), VEGF-A, IP-10, and YKL-40 were measured by enzyme immunoassay before and 6 months after ABC therapy. Disease activity was assessed using DAS28 every 3 months. ABC was infused intravenously according to the standard regimen.Results and discussion. The patients with RA as compared with the control group had significantly elevated levels of IL-6 (2.4 [1.1; 6.4] and 0.7 [0.62; 1.0] pg/ml; p=0.0002), YKL-40 (97 [68.4; 97.9] and 64 [52.4; 107.5] pg/ml; p=0.03), IP-10 (21 [12.9; 49.8] and 14 [9.2; 15.2] pg/ml, respectively; p=0.005). ABC caused a significant decrease in RA activity after 3 months of therapy (p<0.05). Following 6 months, 86% of the patients achieved good and moderate EULAR responses; low RA activity according to DAS28 was recorded in 52%. ABC induced significant decreases in the concentrations of IL-6 to 1.29 [0.9; 2.2] pg/ml (p=0.0006) and IP-10 to 14 [7.5; 28] pg/ml (p=0.007) after 6 months of therapy. A similar trend was observed when assessing changes in the concentration of matrix metalloproteinase 3 (MMP-3), which reduced from 30.1 [13; 82] to 10 [7.4; 55] pg/ml (p=0.0003), and in that of RF, which declined from 218 [9.6; 187] to 159 [9.7; 155] pg/ml (p=0.02). The lower levels of IL-6 (r=0.5) and IP-10 (r=0.32) significantly correlated with a decrease in DAS28 (p<0.05). There was a trend towards a more pronounced reduction in disease activity in patients positive for ACCP and antibodies to modified citrullinated vimentine (AMCV). The percentage of non-responders to therapy in the ACCP- and AMCV-negative groups was nearly twice as high as in those who were positive for these antibodies (27.2 and 16%; 26.7 and 14.8%, respectively), but these differences failed to reach significance. However, after 6-month of follow-up, the percentage of non-respondents in the AMCV-negative group was significantly higher than in the AMCV-positive group (20% and 0%, respectively; p=0.03). The patients who did not respond to ABC therapy had higher baseline levels of IL-6 (p=0.03) and YKL-40 (p=0.02). Conclusion. ABC therapy results in a substantial reduction in the concentration of the proinflammatory cytokines IL-6 and IP-10, as well as MMP-3 and RF. The lower levels of IL-6 and IP-10 significantly correlated with a decrease in RA activity. There was a tendency towards a more pronounced reduction of disease activity in ACCP- and AMCV-positive patients. The high baseline levels of IL-6 and YKL-40 and the absence of AMCV may suggest that ABC therapy can be ineffective.

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“…In view of the possibility of eGFP promoting an immune response in vivo we opted to continue in vivo experiments with BALB/c MSCs. MSCs have broadly similar characteristics across species [54] and it is likely that BALB/c MSCs may migrate to inflamed joints in a similar manner to FVB MSCs. Consistent with data from our group and others, and supported by the hypothesis that MSCs may contribute to disease chronicity, we saw a worsening of clinical disease after treatment with allogeneic BALB/c MSCs.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Murine Mesenchymal Stem Cells: Migration to Inflamed Joints In Vivo and Amelioration of Collagen Induced Arthritis When Transduced to Express CTLA4Ig

Sullivan

Barry

Ritter

et al. 2013

Stem Cells and Development

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Alterations in Cytokine Profile and Dendritic Cells Subsets in Peripheral Blood of Rheumatoid Arthritis Patients before and after Biologic Therapy

Cited by 26 publications

References 35 publications

Patients with the most advanced rheumatoid arthritis remain with Th1 systemic defects after TNF inhibitors treatment despite clinical improvement

Patients with the most advanced rheumatoid arthritis remain with Th1 systemic defects after TNF inhibitors treatment despite clinical improvement

The Effect of Abatacept on Blood Biomarkers in Patients With Rheumatoid Arthritis

Allogeneic Murine Mesenchymal Stem Cells: Migration to Inflamed Joints In Vivo and Amelioration of Collagen Induced Arthritis When Transduced to Express CTLA4Ig

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