Levels of Plasma-soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) Are Correlated with Disease Activity in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 933-938 ◽  
Author(s):  
SANG TAE CHOI ◽  
EUN-JIN KANG ◽  
YOU JUNG HA ◽  
JUNG-SOO SONG
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Myeloid Cells ◽  
Disease Status ◽  
Joint Disease ◽  
Healthy Controls ◽  
Cell Counts ◽  
Tnf Α ◽  
White Blood Cell Counts ◽  
Factor Α

Objective.To determine whether levels of plasma-soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are elevated in patients with rheumatoid arthritis (RA) and whether levels are correlated with disease activity and other variables.Methods.Our study included 71 patients with RA and 50 age- and sex-matched healthy controls. Clinical characteristics and laboratory measures, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and 28-joint Disease Activity Score (DAS28) were assessed. Plasma levels of sTREM-1 and tumor necrosis factor-α (TNF-α) were measured by ELISA.Results.Patients with RA had significantly higher plasma sTREM-1 levels than healthy controls (170.10 ± 84.71 pg/ml vs 97.41 ± 40.64 pg/ml; p < 0.001). In patients with RA, plasma sTREM-1 levels were found to be correlated with DAS28, ESR, CRP, white blood cell counts, neutrophil counts, and plasma TNF-α levels (r = 0.329, p = 0.005; r = 0.241, p = 0.043; r = 0.314, p < 0.001; r = 0.261, p = 0.028; r = 0.278, p = 0.019; and r = 0.313, p = 0.009, respectively). Plasma sTREM-1 levels in patients with active disease status (DAS28 > 3.2) were significantly higher than in those with low disease status (DAS28 ≤ 3.2; 208.89 ± 100.14 pg/ml vs 150.29 ± 68.70 pg/ml; p = 0.005).Conclusion.Patients with RA had higher plasma sTREM-1 levels than healthy controls, and plasma sTREM-1 levels were correlated with disease activity measures, suggesting that plasma sTREM-1 could play a role in the inflammatory process associated with TNF-α, and that it may be a useful disease activity marker in RA.

scholarly journals Effects of Joint Lavage with Dimethylsulfoxide on LPS-Induced Synovitis in Horses—Clinical and Laboratorial Aspects

2020 ◽  
Vol 7 (2) ◽  
pp. 57
Author(s):  
Eric Danilo Pauls Sotelo ◽  
Cynthia Prado Vendruscolo ◽  
Joice Fülber ◽  
Sarah Raphaela Torquato Seidel ◽  
Fernando Mosquera Jaramillo ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Cartilage Degradation ◽  
Cell Counts ◽  
Tnf Α ◽  
Equine Medicine ◽  
Lactated Ringer's Solution ◽  
White Blood Cell Counts ◽  
Factor Α ◽  
Joint Lavage

Several studies in human and equine medicine have produced controversial results regarding the role of dimethylsulfoxide (DMSO) as a therapeutic agent. This study aimed to evaluate the effect of joint lavage with different DMSO concentrations on biomarkers of synovial fluid inflammation and cartilage degradation in joints with lipopolysaccharide (LPS)-induced synovitis. Twenty-six tibiotarsal joints of 13 horses were randomly distributed into four groups (lactated Ringer’s solution; 5% DMSO in lactated Ringer’s; 10% DMSO in lactated Ringer’s; and sham). All animals were evaluated for the presence of lameness, and synovial fluid analyses were performed at 0 h, 1 h, 8 h, 24 h, and 48 h (T0, T1, T8, T24, and T48, respectively). The white blood cell counts (WBC), total protein (TP), urea, prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), hyaluronic acid (HA), and chondroitin sulfate (CS) concentrations were measured. The WBC counts and PGE2, IL-1β, IL-6, and TP concentrations increased in all groups at T8 compared to baseline values (p < 0.05). At T48, only the 5% DMSO and 10% DMSO groups showed a significant decrease in WBC counts (p < 0.05). Furthermore, the 10% DMSO group had lower concentrations of PGE2 and IL-1β at T48 than at T8 (p < 0.05) and presented lower IL-6 levels than the5% DMSO and lactated Ringer’s groups at T24. All groups showed an increase in CS concentration after LPS-induced synovitis. Joint lavage with 10% DMSO in lactated Ringer’s has anti-inflammatory but not chondroprotective effects.

Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in patients with rheumatoid arthritis treated with tumour necrosis factor-α blocking agents

2008 ◽  
Vol 68 (2) ◽  
pp. 249-252 ◽  
Author(s):  
E H Halvorsen ◽  
E A Haavardsholm ◽  
S Pollmann ◽  
A Boonen ◽  
D van der Heijde ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Severe Disease ◽  
Peptidylarginine Deiminase ◽  
Association Analyses ◽  
Peptidylarginine Deiminase 4 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Background:Peptidylarginine deiminase 4 (PAD4) may generate epitopes targeted by anticitrullinated protein antibodies in rheumatoid arthritis (RA). A subset of patients with RA has serum autoantibodies to human recombinant PAD4 (hPAD4). Here, we assessed whether anti-hPAD4 status in RA predicted disease outcome after antitumour necrosis factor (anti-TNF)-α therapy.Methods:We analysed RA sera obtained at baseline (n = 40) and after 1 year on anti-TNF-α therapy (n = 33) for anti-hPAD4 IgG. Association analyses between baseline anti-hPAD status and disease progression were performed.Results:We found that 17 of 40 patients (42.5%) were serum anti-hPAD4 positive at baseline, and the anti-hPAD4 IgG levels were stable over 1 year on anti-TNF-α therapy. At baseline, there were indications that anti-hPAD4 positive patients had more severe disease than the negative patients. After 1 year on anti-TNF-α therapy, the anti-hPAD4 positive patients displayed a persistently elevated disease activity score using 28 joint counts score and increased progression in the van der Heijde–modified Sharp erosion score. Accordingly, more anti-hPAD4 positive than negative patients presented an increase in van der Heijde–modified Sharp erosion scores >0 over 1 year.Conclusions:Anti-hPAD4 IgG can be detected in a subset of RA sera and the levels are stable after initiation of anti-TNF-α therapy. Serum anti-hPAD4 may predict persistent disease activity and radiographic progression in patients with RA receiving anti-TNF-α therapy.

Plasma Adiponectin in Patients with Active, Early, and Chronic Rheumatoid Arthritis Who Are Steroid- and Disease-Modifying Antirheumatic Drug-Naive Compared with Patients with Osteoarthritis and Controls

2009 ◽  
Vol 36 (9) ◽  
pp. 1885-1891 ◽  
Author(s):  
TRINE BAY LAURBERG ◽  
JAN FRYSTYK ◽  
TORKELL ELLINGSEN ◽  
IB T. HANSEN ◽  
ANETTE JØRGENSEN ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Antirheumatic Drug ◽  
Joint Disease ◽  
Healthy Controls ◽  
Plasma Adiponectin ◽  
Activity Measures ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug ◽  
Disease Activity Measures

Objective.Rheumatoid arthritis (RA) is a systemic chronic inflammatory joint disease, whereas osteoarthritis (OA) is a local joint disease with low-level inflammatory activity. The pathogenic role of the adipocytokine adiponectin is largely unknown in these diseases. We hypothesized (1) that plasma adiponectin concentrations differ in healthy controls and patients with early disease-modifying antirheumatic drug (DMARD)-naive RA, chronic RA, and OA; (2) that changes in adiponectin are observed during methotrexate (MTX) treatment of chronic RA; and (3) that adiponectin correlates to disease activity measures in RA.Methods.Plasma adiponectin was analyzed with a validated in-house immunoassay. We measured adiponectin in healthy controls (n = 45) and patients with early DMARD-naive RA (n = 40), chronic RA (n = 74), and OA (n = 35). In a subgroup of patients with chronic RA (n = 31), the longitudinal effect of MTX treatment on adiponectin (Week 0 vs Week 28) was investigated.Results.Adiponectin differed significantly between healthy controls (mean 4.8 ± SD 2.7 mg/l) and the 3 groups, with 8.9 ± 4.8 mg/l in early RA, 11.6 ± 5.6 mg/l in chronic RA, and 14.1 ± 6.4 mg/l in OA. Longitudinally, MTX treatment increased adiponectin significantly from 9.7 ± 4.5 mg/l at Week 0 to 11.0 ± 4.5 mg/l at Week 28 in chronic RA. No correlations to disease activity measures were found.Conclusion.Both early DMARD-naive and chronic RA were associated with higher plasma adiponectin compared to healthy controls, but lower plasma adiponectin than OA. Adiponectin increased 13% during MTX treatment. In patients with RA and OA body mass index, age, sex, and disease activity measures failed to explain the findings.

Circulating Dickkopf-1 Is Correlated with Bone Erosion and Inflammation in Rheumatoid Arthritis

2011 ◽  
Vol 38 (5) ◽  
pp. 821-827 ◽  
Author(s):  
SHI-YAO WANG ◽  
YAN-YING LIU ◽  
HUA YE ◽  
JIAN-PING GUO ◽  
RU LI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Bone Erosion ◽  
Interleukin 1 ◽  
Healthy Controls ◽  
Serum Samples ◽  
Reactive Protein ◽  
Tnf Α ◽  
Factor Α ◽  
Dickkopf 1

Objective.To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA.Methods.Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA.Results.The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10−4) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-α inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01).Conclusion.DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.

Disease Activity Improvement in Rheumatoid Arthritis Treated with Tumor Necrosis Factor-α Inhibitors Correlates with Increased Soluble Fas Levels

2014 ◽  
Vol 41 (10) ◽  
pp. 1961-1965 ◽  
Author(s):  
Eloisa Romano ◽  
Riccardo Terenzi ◽  
Mirko Manetti ◽  
Francesca Peruzzi ◽  
Ginevra Fiori ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Soluble Fas ◽  
Tnf Α ◽  
Before And After ◽  
Factor Α ◽  
Necrosis Factor

Objective.Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia. Tumor necrosis factor-α (TNF-α) plays a pivotal role in RA by interfering with the Fas–Fas ligand (FasL) proapoptotic pathway. We investigated the circulating levels of soluble Fas (sFas) and soluble FasL (sFasL), and their possible correlation with disease activity and improvement after anti-TNF-α treatment in RA.Methods.Serum levels of sFas and sFasL were measured by quantitative ELISA in 52 patients with RA before and after 3 months of anti-TNF-α treatment (adalimumab, n = 32; infliximab, n = 20). Disease activity measures [Disease Activity Score at 28 joints-erythrocyte sedimentation rate (DAS28-ESR), C-reactive protein (CRP)] were recorded before and after treatment. Forty age-matched and sex-matched healthy subjects served as controls.Results.No significant differences in serum sFas levels were detected between anti-TNF-α-naive patients with RA and controls. After anti-TNF-α treatment, serum sFas levels significantly increased in patients with RA compared to both anti-TNF-α-naive patients and controls. Increased sFas levels inversely correlated with disease activity variables (DAS28-ESR: r = −0.739, CRP: r = −0.636, both p < 0.001). No significant differences in sFasL levels were detected in patients with RA before and after anti-TNF-α treatment.Conclusion.In RA, an increase in sFas levels closely correlates with improvement in disease activity induced by TNF-α inhibitors, suggesting their ability to modulate Fas-mediated synoviocyte apoptosis.

scholarly journals CD4+CD25highCD127low/- Treg Cell Frequency from Peripheral Blood Correlates with Disease Activity in Patients with Rheumatoid Arthritis

2011 ◽  
Vol 38 (12) ◽  
pp. 2517-2521 ◽  
Author(s):  
SHIN-YA KAWASHIRI ◽  
ATSUSHI KAWAKAMI ◽  
AKITOMO OKADA ◽  
TOMOHIRO KOGA ◽  
MAMI TAMAI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treg Cell ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Clinical Disease ◽  
Joint Disease ◽  
Healthy Controls ◽  
Cell Frequency ◽  
Clinical Disease Activity

Objective.To investigate whether the frequency of peripheral blood (PB) regulatory T cells (Treg) correlates with the clinical disease activity of rheumatoid arthritis (RA).Methods.PB Treg cells, defined as the CD4+CD25highCD127low/- population, were examined by flow cytometry in 48 patients with RA, including 13 who had never received disease-modifying antirheumatic drugs (DMARD), 19 with active disease who were receiving (n = 14) or had received (n = 5) DMARD, and 16 receiving DMARD whose disease was in remission. The clinical disease activity of the patients was defined by the 28-joint Disease Activity Score (DAS28). The association of DAS28, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) with the frequency of PB Treg cells was examined.Results.The frequency of PB Treg cells in patients with RA was significantly low compared with that of healthy controls (n = 14). Among the 3 populations of patients with RA, Treg cell frequency was lowest in patients with active RA. In contrast, the Treg cell frequency of patients with RA in remission was similar to that of healthy controls. Accordingly, the frequency of CD4+CD25highCD127low/- Treg cells negatively correlated with DAS28, CRP, and ESR in patients with RA.Conclusion.The data suggest that Treg cells, defined as the CD4+CD25highCD127low/- population, may contribute to the pathogenesis of RA and be an indicator of disease activity.

Natural Killer-22 Cells in the Synovial Fluid of Patients with Rheumatoid Arthritis Are an Innate Source of Interleukin 22 and Tumor Necrosis Factor-α

2011 ◽  
Vol 38 (10) ◽  
pp. 2112-2118 ◽  
Author(s):  
JIE REN ◽  
ZHITAO FENG ◽  
ZHUO LV ◽  
XIAOGUANG CHEN ◽  
JUAN LI
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Granzyme B ◽  
Interleukin 22 ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Objective.To determine the role of natural killer (NK)-22 cells in the pathogenesis of rheumatoid arthritis (RA).Methods.Using flow cytometry, the proportions of NK-22 cells and intracellular contents of perforin, granzyme B, and interferon-γ (IFN-γ) were determined in the peripheral blood (PB) and synovial fluid (SF) of patients with RA and healthy individuals. The levels of interleukin 22 (IL-22) and tumor necrosis factor-α (TNF-α) in the NK-22 supernatant and gene expressions were measured using ELISA and QuantiGene Plex assay, respectively. The effect of NK-22 supernatant on the proliferation of fibroblast-like synoviocytes (FLS) and recombinant human IL-22 (rhIL-22) on the production of monocyte chemoattractant protein 1 (MCP-1) by RA FLS was detected using the yellow tetrazolium salt method and ELISA, respectively. The relationship between the proportions of NK-22 cells and disease activity was analyzed.Results.NKp44 and CCR6 were expressed in a larger population of SF NK cells than in the PB NK cells of patients with RA. NK-22 cells produce low content of perforin, granzyme B, and IFN-γ. NK-22 cellsin vitrocan secrete IL-22 and TNF-α and there was increased messenger RNA coding for IL-22 and TNF-α. NK-22 supernatant can induce the proliferation of RA FLS. Addition of IL-22 antibody plus TNF-α antibody inhibited the proliferation of FLS induced by the NK-22 supernatant. Both rhIL-22 1 ng/ml and rhIL-22 10 ng/ml induced the production of MCP-1 by RA FLS. The NK-22 proportions were positively correlated with disease activity.Conclusion.NK-22 cells are increased in patients with RA and might play a role in the pathogenesis of RA through the production of IL-22 and TNF-α. The proportion of NK-22 cells and disease activity were highly correlated.

scholarly journals Plasma Interleukin-37 Is Elevated in Patients with Rheumatoid Arthritis: Its Correlation with Disease Activity and Th1/Th2/Th17-Related Cytokines

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ting Xia ◽  
Xing-feng Zheng ◽  
Bao-hua Qian ◽  
He Fang ◽  
Jun-jie Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Joint Disease ◽  
Healthy Controls ◽  
Suspension Array ◽  
Gm Csf ◽  
Reactive Protein ◽  
Potential Biomarker ◽  
Anti Inflammatory Cytokine

Interleukin- (IL-) 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA) and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP), were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1βwere analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28) and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA.

scholarly journals Continued Benefit of Tocilizumab Plus Disease-modifying Antirheumatic Drug Therapy in Patients with Rheumatoid Arthritis and Inadequate Clinical Responses by Week 8 of Treatment

2014 ◽  
Vol 41 (2) ◽  
pp. 216-226 ◽  
Author(s):  
Edward C. Keystone ◽  
Andrew Anisfeld ◽  
Sarika Ogale ◽  
Jenny N. Devenport ◽  
Jeffrey R. Curtis
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Response ◽  
Antirheumatic Drug ◽  
Joint Disease ◽  
Phase Iii ◽  
Link Type ◽  
Disease Modifying ◽  
Factor Α ◽  
Disease Modifying Antirheumatic Drug

Objective.To evaluate whether patients with rheumatoid arthritis who did not respond sufficiently to tocilizumab (TCZ) plus disease-modifying antirheumatic drug (DMARD) treatment by Week 8 responded at later timepoints when continuing to take their original dose of TCZ.Methods.In this posthoc analysis of data from phase III randomized controlled trials of inadequate responders (IR) to DMARD or tumor necrosis factor-α inhibitors (anti-TNF), percentages of patients meeting early response criteria were calculated by randomized treatment arm (TCZ 4 mg/kg, 8 mg/kg, or placebo in combination with DMARD). Percentages of patients achieving certain disease activity thresholds at later timepoints were calculated for patients who had/had not achieved response by Week 8.Results.In DMARD-IR early nonresponders, 29.0%, 17.2%, and 3.7% of TCZ 8 mg/kg-randomized, TCZ 4 mg/kg-randomized, and placebo-randomized patients, respectively, achieved 28-joint Disease Activity Score (DAS28) ≤ 3.2 by Week 24. Among anti-TNF-IR patients without early response, 26.5%, 8.5%, and 1.9% of TCZ 8 mg/kg-randomized, TCZ 4 mg/kg-randomized, and placebo-randomized patients, respectively, achieved DAS28 ≤ 3.2 at Week 24.Conclusion.A substantial number of DMARD-IR patients taking TCZ 4 or 8 mg/kg and anti-TNF-IR patients taking TCZ 8 mg/kg who failed to respond by 8 weeks benefited from continued TCZ treatment in combination with DMARD. In contrast, the anti-TNF-IR patients without early responses who continued to take TCZ 4 mg/kg were unlikely to experience a cumulative benefit. ClinicalTrials.gov registration numbers: NCT00106548, NCT00106574, NCT00106535, NCT00106522.

Elevated expression of FABP4 is associated with disease activity in rheumatoid arthritis patients

2020 ◽  
Vol 14 (15) ◽  
pp. 1405-1413
Author(s):  
Shuaishuai Chen ◽  
Juping Du ◽  
Weibo Zhao ◽  
Rong Cao ◽  
Na Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Disease Activity Score ◽  
High Disease Activity ◽  
Joint Disease ◽  
Activity Score ◽  
Healthy Controls ◽  
Receiver Operating

Aim: Data from 124 rheumatoid arthritis (RA) patients and 69 healthy controls were collected. Materials & methods: ELISA was performed to detect serum FABP4 levels. Results: FABP4 level was elevated in RA patients and positively associated with 28-joint disease activity score, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, total cholesterol, triglyceride and low-density lipoprotein cholesterol. Additionally, the area under the receiver operating characteristic curve for FABP4 was 0.685 for RA patients versus healthy controls (p = 0.001). RA patients were separated into low, moderate and high disease activity based on 28-joint disease activity score. The area under the receiver operating characteristic value was 0.877 for RA patients with high disease activity versus healthy controls (p < 0.001). Conclusion: FABP4 was associated with disease activity in RA patients.

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