scholarly journals The relationship of blood CDC42 level with Th1 cells, Th17 cells, inflammation markers, disease risk/activity, and treatment efficacy of rheumatoid arthritis

2021 ◽  
Author(s):  
Yongji Li ◽  
Wendi Yang ◽  
Feng Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Treatment Efficacy ◽  
Th17 Cells ◽  
Immune Cell ◽  
Disease Risk ◽  
Th1 Cells ◽  
Clinical Role ◽  
Reactive Protein

Abstract Background Cell division control protein 42 (CDC42) is reported to be involved in multiple inflammation processes by regulating T cell differentiation, maintaining immune cell homeostasis, and altering their function, while no relevant studies explored its clinical role in patients with rheumatoid arthritis (RA). Therefore, this study aimed to explore the correlation of CDC42 with Th1 and Th17 cells and its association with disease risk, activity, and treatment outcomes of RA. Methods After the enrollment of 95 active RA patients and 50 healthy subjects (HC), their CDC42, Th1 cells, and Th17 cells were assayed by RT-qPCR and flow cytometry, accordingly. For RA patients only, CDC42 was also detected at W6, and W12 after treatment. The treatment response and remission status were evaluated at W12. Results Compared to HC, CDC42 was reduced (P < 0.001), while Th1 cells (P = 0.021) and Th17 cells (P < 0.001) were increased in RA patients. Besides, CDC42 was negatively correlated with Th17 cells (P < 0.001), erythrocyte sedimentation rate (ESR) (P = 0.012), C-reactive protein (P = 0.002), and disease activity score in 28 joints (DAS28) (P = 0.007), but did not relate to Th1 cells or other disease features (all P > 0.05) in RA patients. Furthermore, CDC42 was elevated during treatment in RA patients (P < 0.001). Moreover, CDC42 increment at W12 correlated with treatment response (P = 0.004). Besides, CDC42 elevation at W0 (P = 0.038), W6 (P = 0.001), and W12 (P < 0.001) also linked with treatment remission. Conclusion CDC42 has the potential to serve as a biomarker to monitor disease activity and treatment efficacy in patients with RA.

scholarly journals Diminished cytokine-induced Jak/STAT signaling is associated with rheumatoid arthritis and disease activity

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244187
Author(s):  
Jason Ptacek ◽  
Rachael E. Hawtin ◽  
Dongmei Sun ◽  
Brent Louie ◽  
Erik Evensen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Peripheral Blood Mononuclear ◽  
Immune Cell Subsets ◽  
Systems Immunology ◽  
Stat Signaling ◽  
Multiple Cell

Rheumatoid arthritis (RA) is a systemic and incurable autoimmune disease characterized by chronic inflammation in synovial lining of joints. To identify the signaling pathways involved in RA, its disease activity, and treatment response, we adapted a systems immunology approach to simultaneously quantify 42 signaling nodes in 21 immune cell subsets (e.g., IFNα→p-STAT5 in B cells) in peripheral blood mononuclear cells (PBMC) from 194 patients with longstanding RA (including 98 patients before and after treatment), and 41 healthy controls (HC). We found multiple differences between patients with RA compared to HC, predominantly in cytokine-induced Jak/STAT signaling in many immune cell subsets, suggesting pathways that may be associated with susceptibility to RA. We also found that high RA disease activity, compared to low disease activity, was associated with decreased (e.g., IFNα→p-STAT5, IL-10→p-STAT1) or increased (e.g., IL-6→STAT3) response to stimuli in multiple cell subsets. Finally, we compared signaling in patients with established, refractory RA before and six months after initiation of methotrexate (MTX) or TNF inhibitors (TNFi). We noted significant changes from pre-treatment to post-treatment in IFNα→p-STAT5 signaling and IL-10→p-STAT1 signaling in multiple cell subsets; these changes brought the aberrant RA signaling profiles toward those of HC. This large, comprehensive functional signaling pathway study provides novel insights into the pathogenesis of RA and shows the potential of quantification of cytokine-induced signaling as a biomarker of disease activity or treatment response.

scholarly journals A Systems Immunology Approach Identifies Cytokine-Induced STAT Signaling Pathways Critical to Rheumatoid Arthritis Disease Activity and Treatment Response

2019 ◽  
Author(s):  
Jason Ptacek ◽  
Rachael E. Hawtin ◽  
Dongmei Sun ◽  
Brent Louie ◽  
Erik Evensen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Disease Activity ◽  
Signaling Pathways ◽  
Treatment Response ◽  
Immune Cell ◽  
Rheumatoid Arthritis Disease ◽  
Immune Cell Subsets ◽  
Systems Immunology ◽  
Stat Signaling

AbstractRheumatoid arthritis (RA), a chronic autoimmune disease characterized by circulating autoantibodies, involves many cytokine-mediated signaling pathways in multiple immune cell subsets. Most studies of immune cells in RA have limitations, such as analysis of a small number of cell subsets or pathways, and limited longitudinal data on patient phenotypes. In this study, we used an innovative systems immunology approach to simultaneously quantify up to 882 signaling nodes (Jak/STAT signaling readouts modulated by cytokines and other stimuli) in 21 immune cell subsets. We studied 194 RA patients and 41 controls, including 146 well-characterized RA patients prior to, and 6 months after, initiation of methotrexate or biologic agents from the Treatment Efficacy and Toxicity in RA Database and Repository (TETRAD). There was strikingly attenuated signaling capacity in RA patients in IFNα stimulation followed by measurement of phosphorylated STAT1 [IFNα→p-STAT1] in six immune cell subsets. Multiple nodes showed negative association with disease activity, including IFNα→STAT5 signaling in naive and memory B cells. In contrast, IL-6-induced STAT1 and STAT3 activation in central memory CD4-negative T cells showed a positive association with disease activity. Multiple nodes were associated with treatment response, including IFNα→STAT1 in monocytes and IL-6→STAT3 in CD4+ naive T cells. Decision tree analysis identified a model combining these two nodes as a high-performing classifier of treatment response to TNF inhibitors. Our study provides novel information on RA disease mechanisms and serves as a framework for the discovery and validation of biomarkers of treatment response in RA.

scholarly journals Serum etanercept concentrations in relation to disease activity and treatment response assessed by ultrasound, biomarkers and clinical disease activity scores: results from a prospective observational study of patients with rheumatoid arthritis

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001985
Author(s):  
Johanna Elin Gehin ◽  
Silje Watterdal Syversen ◽  
David John Warren ◽  
Guro Løvik Goll ◽  
Joseph Sexton ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Observational Study ◽  
Disease Activity ◽  
Treatment Response ◽  
Therapeutic Range ◽  
Power Doppler ◽  
Therapeutic Drug ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Markers Of Inflammation

ObjectivesTo identify the therapeutic range for etanercept and to assess the incidence of anti-etanercept antibody formation.MethodsAssociations between etanercept serum concentration and disease activity as well as treatment response were examined in a longitudinal observational study of rheumatoid arthritis patients starting etanercept. Disease activity was assessed by ultrasound (grey scale and power Doppler), 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index, plasma calprotectin and C reactive protein. Etanercept concentration and anti-etanercept antibodies were analysed using automated in-house fluorescence assays.ResultsA total of 89 patients were included, whereof 66% were biological disease-modifying antirheumatic drug (DMARD) naïve and 91% used concomitant synthetic DMARD. At 3 months, the median etanercept concentration was 1.8 (IQR 1.1–2.5) mg/L. Longitudinal associations were found between etanercept concentration and disease activity assessed by plasma calprotectin, C reactive protein and DAS28, but not between etanercept concentration and improvement in disease activity by any of the parameters at 3, 6 or 12 months of treatment. Etanercept concentrations were not significantly different among patients who achieved response or remission, compared with non-response or non-remission. Hence, no therapeutic range could be identified. None of the patients developed anti-etanercept antibodies.ConclusionDespite the use of sensitive and objective markers of inflammation, a therapeutic range could not be identified for etanercept. Hence, this study suggests that proactive therapeutic drug monitoring is unlikely to benefit rheumatoid arthritis patients treated with etanercept, but a potential benefit in certain clinical situations cannot be excluded.

scholarly journals AB0031 T HELPER 17 CELLS WERE SIGNIFICANTLY DECREASED BY MITOCHONDRIAL ELECTRON TRANSPORT CHAIN COMPLEX INHIBITOR IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1318.2-1318
Author(s):  
H. R. Lee ◽  
S. J. Yoo ◽  
J. Kim ◽  
I. S. Yoo ◽  
C. K. Park ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Electron Transport ◽  
Disease Activity ◽  
Th17 Cells ◽  
Electron Transport Chain ◽  
Chain Complex ◽  
Complex Iii ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain ◽  
Healthy Control

Background:Reactive oxygen species (ROS) and T helper 17 (TH17) cells have been known to play an important role in the pathogenesis of rheumatoid arthritis (RA). However, the interrelationship between ROS and TH17 remains unclear in RAObjectives:To explore whether ROS affect TH17 cells in peripheral blood mononuclear cells (PBMC) of RA patients, we analyzed ROS expressions among T cell subsets following treatment with mitochondrial electron transport chain complex inhibitors.Methods:Blood samples were collected from 40 RA patients and 10 healthy adult volunteers. RA activity was divided according to clinical parameter DAS28. PBMC cells were obtained from the whole blood using lymphocyte separation medium density gradient centrifugation. Following PBMC was stained with Live/Dead stain dye, cells were incubated with antibodies for CD3, CD4, CD8, and CD25. After fixation and permeabilization, samples were stained with antibodies for FoxP3 and IL-17A. MitoSox were used for mitochondrial specific staining.Results:The frequency of TH17 cells was increased by 4.83 folds in moderate disease activity group (5.1>DAS28≥3.2) of RA patients compared to healthy control. Moderate RA activity patients also showed higher ratio of TH17/Treg than healthy control (3.57 folds). All RA patients had elevated expression of mitochondrial specific ROS than healthy control. When PBMC cells were treated with 2.5uM of antimycin A (mitochondrial electron transport chain complex III inhibitor) for 16 h, the frequency of TH17 cells was significantly decreased.Conclusion:The mitochondrial electron transport chain complex III inhibitor markedly downregulated the frequency of TH17 cells in moderate disease activity patients with RA. These findings provide a novel approach to regulate TH17 function in RA through mitochondrial metabolism related ROS production.References:[1]Szekanecz, Z., et al., New insights in synovial angiogenesis. Joint Bone Spine, 2010. 77(1): p. 13-9.[2]Prevoo, M.L., et al., Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum, 1995. 38(1): p. 44-8.Disclosure of Interests:None declared

scholarly journals Interleukin-37 as an anti-inflammatory cytokine: does its relation to disease activity suggest its potential role in rheumatoid arthritis therapy?

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Eman A. Baraka ◽  
Mona G. Balata ◽  
Shereen H. Ahmed ◽  
Afaf F. Khamis ◽  
Enas A. Elattar
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Tender Joint ◽  
Cross Sectional ◽  
Reactive Protein ◽  
Significant Difference ◽  
The Mean ◽  
Anti Inflammatory

Abstract Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.

Multiple time-point assessment of lncRNA MEG3 shows potential to monitor treatment efficacy in rheumatoid arthritis patients

2021 ◽  
Author(s):  
Zehui Wang ◽  
Weiyong Zhang ◽  
Shouxia Li ◽  
Dingli Chen ◽  
Lei Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood ◽  
Treatment Efficacy ◽  
Multiple Time ◽  
Clinical Role ◽  
Multiple Time Point ◽  
Potential Biomarker ◽  
Monitoring Treatment ◽  
Time Point

Background: This study explored the clinical role of lncRNA MEG3 in rheumatoid arthritis (RA) management. Materials & methods: Totally, 191 active RA patients were enrolled, and their lncRNA MEG3 expressions in peripheral blood monoclonal cells were detected. Results: LncRNA MEG3 expression was downregulated, and it negatively correlated with lesion joints, inflammation and disease activity in RA patients. Moreover, lncRNA MEG3 expression was increased during treatment; meanwhile its increment correlated with treatment response and remission. Conclusion: LncRNA MEG3 may serve as a potential biomarker for monitoring treatment efficacy in RA management.

FRI0126 POOR ADHERENCE TO METHOTREXATE IS ASSOCIATED WITH PERSISTENT DISEASE ACTIVITY DURING FOLLOW-UP FOR RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 644.1-645
Author(s):  
J. H. Kang ◽  
S. E. Choi ◽  
H. Xu ◽  
D. J. Park ◽  
S. S. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Outcome ◽  
Disease Activity ◽  
Reactive Protein ◽  
Rate Score ◽  
Tertiary Center ◽  
Proportion Of Days Covered ◽  
Euroqol 5D ◽  
Control Disease

Objectives:Although methotrexate (MTX) is the cornerstone therapy in patients with rheumatoid arthritis (RA), adherence to MTX in these patients is typically suboptimal. Thus, we investigated the proportion of RA patients who were adherent to MTX and whether non-adherence to MTX affected the clinical outcome in these patients during follow-up.Methods:We enrolled 331 RA patients from a single tertiary center. Data were collected at the time of enrollment and then annually for 4 consecutive years. Adherence was defined by the proportion of days covered at 1 year. Patients were divided into two groups: patients who took more than 80% of MTX and those who did not. Univariate and multivariate analyses were performed to identify the association between drug compliance and clinical outcome.Results:Of the 331 RA patients, 8.7% had taken less than 80% of MTX during the follow-up period. Non-adherent patients had lower EuroQol-5D scores (P=0.013) and higher RAPID3 scores (P=0.004) at baseline than adherent patients. Leflunomide was more commonly prescribed to adherent patients than non-adherent patients (P=0.012). Non-adherent patients had a higher mean Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate score (P=0.001), higher mean DAS28-C-reactive protein (CRP) score (P=0.001), and higher mean rate of tender and swollen joints (P=0.003 and P=0.002, respectively) than adherent patients. In the multivariate analysis, poor MTX adherence was significantly associated with a higher mean DAS28-CRP score (odds ratio, 0.270; 95% confidence interval, 0.165–0.444; P<0.001).Conclusion:Adherence to MTX can affect disease activity during follow-up in Korean patients with RA. Our results provide a rationale for patient education to maintain good drug adherence in RA patients, to control disease activity.Disclosure of Interests:None declared

scholarly journals Effects of Antitumor Necrosis Factor Therapy on Osteoprotegerin, Neopterin, and sRANKL Concentrations in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Kurz ◽  
Manfred Herold ◽  
Elisabeth Russe ◽  
Werner Klotz ◽  
Guenter Weiss ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Systemic Autoimmune Disease ◽  
Das28 Score ◽  
Reactive Protein ◽  
Adalimumab Therapy ◽  
Receptor Activator ◽  
Joint Erosions ◽  
Factor Therapy ◽  
Necrosis Factor

Background. Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation.Methods. 20 female patients with moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs.Results. Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin (rs=0.494,p=0.027), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (bothp<0.02). Patients who achieved remission (n=7) or showed a good response according to EULAR criteria (n=13) presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment (p=0.018for remission,p=0.011for good response).Conclusions. Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades.

Sign in / Sign up

Export Citation Format

Share Document