scholarly journals Serum Matrix Metalloproteinase-3 in Comparison with Acute Phase Proteins as a Marker of Disease Activity and Radiographic Damage in Early Rheumatoid Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Mahmood M. T. M. Ally ◽  
Bridget Hodkinson ◽  
Pieter W. A. Meyer ◽  
Eustasius Musenge ◽  
Mohammed Tikly ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinase ◽  
Disease Activity ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Activity Index ◽  
Acute Phase Reactants ◽  
Matrix Metalloproteinase 3 ◽  
Early Ra ◽  
Potential Biomarker

Matrix metalloproteinase-3 (MMP-3) is involved in the immunopathogenesis of rheumatoid arthritis (RA), but little is known about its relationship to genetic susceptibility and biomarkers of disease activity, especially acute phase reactants in early RA. MMP-3 was measured by ELISA in serum samples of 128 disease-modifying, drug-naïve patients and analysed in relation to shared epitope genotype, a range of circulating chemokines/cytokines, acute phase reactants, autoantibodies, cartilage oligomeric protein (COMP), and the simplified disease activity index (SDAI). MMP-3 was elevated >1.86 ng/ml in 56.25% of patients (P<0.0001), correlated with several biomarkers, notably IL-8, IL-6, IFNγ, VEGF and COMP (rvalues = 0.22–0.33,P<0.014–0.0001) and with CRP and SAA levels (r=0.40and 0.41, resp.,P<0.0000) and SDAI (r=0.29,P<0.0001), but not with erosions or nodulosis. However, the correlations of CRP and SAA with SDAI were stronger (respective values of 0.63 and 0.54,P<0.001for both). COMP correlated with smoking, RF, and MMP-3. MMP-3 is significantly associated with disease activity, inflammatory mediators and cartilage breakdown, making it a potential biomarker of disease severity, but seemingly less useful than CRP and SAA as a biomarker of disease activity in early RA.

scholarly journals Serum and synovial fluid levels of matrix metalloproteinase-3 as a biomarker of joint damage in patients with rheumatoid arthritis

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
E A Hafez ◽  
S A Elbakry ◽  
M A Abdelrahman ◽  
H M Sakr ◽  
N A Mohamed ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinase ◽  
Disease Activity ◽  
Healthy Volunteers ◽  
Joint Damage ◽  
Serum Levels ◽  
Common Disease ◽  
Special Role ◽  
Matrix Metalloproteinase 3 ◽  
Early Ra

Abstract Background Rheumatoid arthritis (RA) is one of the systemic autoimmune diseases characterized by chronic synovitis and progressive joint destruction leading to decline in functional capacity, eventual work disability, and reduced quality of life. Considering the common disease activity indicators are unspecific for arthritis, novel biomarkers have been rapidly developed for predicting structural destruction progression in RA. Matrix metalloproteinase-3 plays a special role in rheumatoid arthritis pathogenesis and has been suggested as a marker of disease activity and joint damage. Patients and Methods MMP-3 was measured by ELISA in serum samples of 40 early RA patients and compared to age and sex matched control group of 40 healthy volunteers. Synovial levels of MMP-3 were measured only in 8 RA patients, who were indicated for knee arthrocentesis. Joint damage was assessed using SENS score on plain radiography. Results Serum MMP-3 levels were significantly higher in RA patients than healthy volunteers (P-value &lt;0.001). Measured synovial levels of MMP-3 were significantly correlated to the serum levels. There were statistically significant positive correlations between serum MMP-3 with RF titers, AntiCCP titres, CRP, and DAS28 -ESR activity score. There was no significant correlation to total SENS score. ROC curve was used to define the best cut off value of serum MMP3 to discriminate between RA and healthy controls, which was found to be &gt;50ng/ml. Conclusion Serum levels of MMP-3 can be used as noninvasive biomarker of RA, and also indicator of disease activity in early RA patients.

THU0620-HPR MEASUREMENT OF LOW DISEASE ACTIVITY USING THE CLINICAL DISEASE ACTIVITY INDEX (CDAI) VERSUS THE DISEASE ACTIVITY SCORE 28 (DAS 28): IMPACT OF INFLAMMATION MARKERS ON THE COMPARATIVE EFFECTIVENESS OF BIOLOGICS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 553.1-553
Author(s):  
K. Janke ◽  
K. Biester ◽  
D. Krause ◽  
B. Richter ◽  
C. Schürmann ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Comparative Effectiveness ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Disease Activity Index ◽  
Signs And Symptoms ◽  
Acute Phase Reactants ◽  
Das 28 ◽  
Effectiveness Studies

Background:Biologics for the treatment of rheumatoid arthritis (RA) have different modes of action to target auto-inflammatory processes causing the signs and symptoms of the disease. Different biologics may thus have different effects on inflammatory markers. For instance, previous studies have shown that the interleukin-6-inhibitor tocilizumab (TOC) decreases the level of acute phase reactants (APRs) [1]. Such direct effects on inflammatory markers may lead to an overestimation of clinical response if disease activity is measured via scores including inflammatory markers, such as the Disease Activity Score 28 (DAS 28). The detected changes in disease activity may not adequately reflect the clinical improvement of signs and symptoms.Objectives:In our study, we compared biologics with each other using two different disease activity scores: the DAS 28 including APRs and the clinical disease activity index (CDAI) excluding APRs. The aim of this study was to assess whether the use of the two different scores affects comparative effectiveness studies on biologics for the treatment of RA.Methods:We compared results on the comparative effectiveness of biologics using the corresponding thresholds for low disease activity (LDA) for the DAS 28 (< 3.2) and the CDAI (≤ 10). We performed two separate network meta-analyses (NMAs) after a thorough step-by-step evaluation of the similarity, homogeneity and consistency assumptions of the patient populations and the study data.Our study formed part of a systematic review (including NMAs) that was largely based on clinical study reports and re-analyses of LDA using individual patient data provided by sponsors for studies conducted up to 2017. Thus, the analyses include hitherto unknown data on LDA analysed by means of the CDAI, especially data from older studies. An extensive comparison of DAS 28 and CDAI in different patient populations was possible.Results:For all analysed patient populations, comparisons of TOC versus other biologics yielded remarkable results: advantages for TOC were found in NMAs using the DAS 28, which were not confirmed in NMAs using the CDAI. For methotrexate (MTX)-naïve patients, using the DAS 28, TOC showed a greater benefit than abatacept (ABA), certolizumab pegol (CZP), and etanercept (ETA), which was not confirmed by the CDAI. In contrast, TOC showed less benefit than adalimumab (ADA) and ETA. For patients after MTX failure and using the DAS 28, TOC showed a greater benefit than ABA, ADA, anakinra (ANA), ETA, golimumab (GOL), and infliximab (INF). With the exception of ANA, these advantages were not confirmed by the CDAI. Similar differences between DAS 28 and CDAI were shown in patients treated with biologics in monotherapy or after failure of biologics.Conclusion:In comparative effectiveness studies of biologics, the assessment of LDA using the DAS 28 instead of the CDAI leads to a consistent overestimation of the benefit of TOC in all patient populations, regardless of pre-treatment or combined therapy with MTX. The inclusion of APRs in disease activity scores may thus introduce bias. A score excluding inflammatory markers should therefore be used to ensure valid results.References:[1]Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum 2011; 63(1): 43-52.Disclosure of Interests:Kirsten Janke: None declared, Katharina Biester: None declared, Dietmar Krause Grant/research support from: Pfizer and AbbVie (Abbott), Bernd Richter: None declared, Christoph Schürmann: None declared, Katharina Hirsch: None declared, Beate Wieseler: None declared

Biomarkers in Remission According to Different Criteria in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 42 (11) ◽  
pp. 2066-2070 ◽  
Author(s):  
Sibel Yilmaz-Oner ◽  
Gulsen Ozen ◽  
Meryem Can ◽  
Pamir Atagunduz ◽  
Haner Direskeneli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Type I Collagen ◽  
Activity Index ◽  
Disease Activity Index ◽  
Type Ii Collagen ◽  
Serum Levels ◽  
Type I ◽  
Matrix Metalloproteinase 3 ◽  
Das28 Remission

Objective.Remission is the primary aim in the treatment of patients with rheumatoid arthritis (RA). In this study, we aimed to evaluate biomarker profiles of patients in remission by different criteria and compare these profiles with controls.Methods.Serum levels of calprotectin, interleukin 6 (IL-6), type II collagen helical peptide, C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases (ICTP), matrix metalloproteinase 3 (MMP-3), resistin, and leptin were measured by ELISA in 80 patients. The patients were in Disease Activity Score at 28 joints with erythrocyte sedimentation rate (DAS28-ESR) remission, and had these characteristics: female/male 54/26, mean age 51.4 ± 12.1 years, mean disease duration 11.4 ± 8.1 years, rheumatoid factor positivity 68.7% (n = 55), anticyclic citrullinated peptide positivity 60.7% (n = 48). These patients were also evaluated for the American College of Rheumatology/European League Against Rheumatism (Boolean) and Simple Disease Activity Index (SDAI) remissions. Additionally, 80 age-, sex-, and comorbidity-matched individuals without rheumatic diseases were included in the study as controls.Results.At recruitment of 80 patients in DAS28 remission, 33 patients (41.2%) were found in Boolean remission and 39 patients (48.7%) were in SDAI remission. Serum MMP-3, ICTP, resistin, and IL-6 levels of the 80 patients in DAS28 remission were statistically significantly higher than the controls. Patients in Boolean and SDAI remissions had significantly higher serum ICTP, resistin, and IL-6 levels in comparison with the controls.Conclusion.The 3 commonly used remission criteria of RA are almost similar with regard to patients’ biomarker levels. Biomarker profiles of patients may provide complementary information to clinical evaluation of remission and may help to determine the patients under the risk of progression.

scholarly journals Potential applicability of cytokines as biomarkers of disease activity in rheumatoid arthritis: Enzyme-linked immunosorbent spot assay-based evaluation of TNF-α, IL-1β, IL-10 and IL-17A

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246111
Author(s):  
Keerthie Dissanayake ◽  
Chandrika Jayasinghe ◽  
Priyani Wanigasekara ◽  
Ajith Sominanda
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Elispot Assay ◽  
Disease Activity Score ◽  
Activity Index ◽  
Pivotal Role ◽  
Activity Score ◽  
Early Ra ◽  
Tnf Α ◽  
Potential Applicability

Biomarkers play a pivotal role in the management of rheumatoid arthritis (RA) by facilitating early diagnosis and ‘treat to the target.’ However, no gold standard biomarker has been identified for monitoring the disease activity in RA. Cytokines, a diverse group of small protein molecules secreted by peripheral blood mononuclear cells (PBMCs), play a pivotal role in pathogenesis and disease progression in RA. Research is currently underway to find out the applicability of cytokines as biomarkers in RA. This study aimed to quantify the PBMCs that secrete four types of cytokines; TNF-α, IL-1β, IL-10 and IL-17A in two cohorts of active RA patients (early RA patients and established RA patients), compared to healthy controls (HC), using the enzyme-linked immunosorbent spot (ELISPOT) assay, and to assess their association with measures of disease activity of RA. Patients were recruited from outpatient rheumatology clinics, and the disease activity was assessed using single and composite measures of disease activity. The cytokine expression was evaluated using freshly separated PBMCs from whole blood of RA patients using the ELISPOT assay. The number of PBMCs (counted as spot-forming cells (SFCs) per 105 PBMCs) that secreted the cytokine of interest were statistically significantly higher in early RA patients, compared to HC, for IL-17A (P<0.05). Such an increased number of SFCs was not observed in the established RA group, compared to controls, for any of the cytokines tested. The correlation analysis showed that IL-17A is having a moderate correlation (Spearman`s ρ, p <0.05) with five clinical measures of disease activity, including disease activity score 28 (DAS28). According to the multivariable linear regression models, IL17A was a good predictor of both the disease activity score 28 (DAS28) and clinical disease activity index (CDAI). In conclusion, IL-17A has potential applicability as a biomarker of disease activity of RA.

Relationship Between Some Acute Phase Reactants and the Bath Ankylosing Spondylitis Disease Activity Index in Patients with Ankylosing Spondylitis

2004 ◽  
Vol 97 (4) ◽  
pp. 350-353 ◽  
Author(s):  
Kadir Yildirim ◽  
Akin Erdal ◽  
Saliha Karatay ◽  
Meltem Alkan Melikoğlu ◽  
Mahir Uğur ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Acute Phase ◽  
Activity Index ◽  
Disease Activity Index ◽  
Acute Phase Reactants

scholarly journals Association of Angiogenic and Inflammatory Markers with Power Doppler Ultrasound Vascularity Grade and DAS28-CRP in Early Rheumatoid Arthritis: A Comparative Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Sanchaita Misra ◽  
Sumantro Mondal ◽  
Sudipta Chatterjee ◽  
Aharna Guin ◽  
Pradyot Sinhamahapatra ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Power Doppler ◽  
Significant Rise ◽  
High Disease Activity ◽  
Power Doppler Ultrasonography ◽  
Early Ra ◽  
Grade 3

Objective. Upregulation of various proinflammatory and angiogenic mediators orchestrates the typical pathological synovial alterations in rheumatoid arthritis (RA). DAS28-CRP is commonly used for assessment of RA disease activity and power Doppler ultrasonography (PDUS) is an important modality for assessing synovial vascularity. This study was intended to look for the association of various inflammatory and angiogenic mediators, with respect to different PDUS vascularity grades and disease activity status, in early RA patients. Methods. 50 early RA patients (<6 months disease duration) with either moderate or high disease activity and 30 healthy controls were included in this study. RA patients were subcategorized based on PDUS vascularity grading of wrist joints. Serum levels of proinflammatory cytokines [tumor necrosis factor-α (TNF- α); interleukin-6(IL-6)] and angiogenic markers [angiopoietin-1 and 2 (Ang-1 and Ang-2); vascular endothelial growth factor (VEGF) ] were measured and compared among different patient subgroups. Results. Among 50 patients, 22 and 28 patients had moderate and high DAS28-CRP score, respectively. Patients with grade 3 PDUS score, even with moderate DAS value, showed a significant rise in Ang-1 (p<0.02), VEGF (p<0.008), Ang-2 (p <0.001), and TNF-α (p<0.005) level compared to grade 2 PDUS patients with high DAS values. Conclusion. Higher serum level of angiogenic and inflammatory markers was noted among patients with moderate disease activity but with advanced PDUS vascularity (grade 3) in comparison to high disease activity group with less severe PDUS vascularity (grade 2). PDUS vascularity grading better reflects some markers of angiogenesis and inflammation, than composite disease activity index.

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