Neutral endopeptidase (3.4.24.11) in plasma and synovial fluid of patients with rheumatoid arthritis. A marker of disease activity or a regulator of pain and inflammation?

1993 ◽  
Vol 13 (1) ◽  
pp. 1-4 ◽  
Author(s):  
M. Matucci-Cerinic ◽  
A. Lombardi ◽  
G. Leoncini ◽  
A. Pignone ◽  
L. Sacerdoti ◽  
...  
2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 522.3-523
Author(s):  
R. Shumnalieva ◽  
D. Kachakova ◽  
R. Kaneva ◽  
Z. Kolarov ◽  
S. Monov

Background:MicroRNAs (miRNAs) are a class of small, non-coding RNAs that negatively regulate gene expression at posttranscriptional level. In rheumatoid arthritis studies have shown that miRNA are differentially expressed systemically as well as locally in the inflamed joints [1,2]. The correlation between their systemic or local expression levels and scores for disease activity and progression in RA make them possible candidate for biomarkers in the clinical practice.Objectives:To analyze the expression levels of miR-155 and miR-223 in synovial fluid (SF) from RA patients in regard to the ultrasound scores for disease activity.Methods:A total number of 48 RA patients according to the 1987 ACR criteria were included in the study. Expression levels of miR-155 and miR-223 SF were determined by qPCR (SybrGreen technology) and compared to healthy controls (HCs). Relative changes of gene expression levels of the studied miRNAs were calculated by 2-ΔΔCt method. Musculoskeletal ultrasound (MSUS) examination was performed by two independent examiners on ESAOTE, MyLab60 using both grey scale and power Doppler technic. A semi-quantitative assessment of the peripheral joints was performed for detecting joint inflammation and determining the grade of synovial thickening and the degree of vascularization. Ultrasound features for active disease were correlated to the local expression of the studied miRNAs. SPSS was used for statistical analysis.Results:RA SF showed overexpression of miR-155 (in 79.17%, p=1.63x10-4) and of miR-223 (in 79.17%, p=1.64x10-3) when compared to HCs and both miRNAs could be used to differentiate RA patients from HCs (р=8.0х10-5 and р=2.8х10-4, respectively). When we analyzed the correlation between the diagnosis, the expression of miRNAs and the changes on the musculoskeletal ultrasound examination we found a statistically significant correlation between the presence of synovitis and the degree of the power Doppler signal on MSUS and the local expression of miR-223 (p=6.19 x 10-4 and p=0.003, respectively). SF levels of miR-223 correlated also with the degree of synovial hypertrophy on MSUS (p=0.013). The results for miRNA-155 were not statistically significant.Conclusion:The correlation between the local expression of miR-223 and the ultrasound features of active joint inflammation shows that this miRNA might be a better candidate for local disease biomarker than miR-155. Further analysis with larger sets is needed to confirm if altered local miRNA expression could be used in the clinical practice as biomarker for disease activity especially in cases with subclinical synovitis.References:[1]Filková M, Aradi B, Šenolt L, et al. Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis. ARD, 2014; 73: 1898-1904.[2]Kriegsmann, M., Randau, T.M., Gravius, S. et al. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis. Virchows Arch, 2016; 469, 93–100.Acknowledgements:The study was supported by Grant 14-D/2012 and Grant 60/2013 funded by Medical University-Sofia.Disclosure of Interests:Russka Shumnalieva: None declared, Darina Kachakova: None declared, Radka Kaneva: None declared, Zlatimir Kolarov Speakers bureau: Amgen, Pfizer, Novartis, Abbvie, Roche, Astra-Zeneka, Simeon Monov Speakers bureau: Amgen, Pfizer, Novartis, Abbvie, Roche, Astra-Zeneka


2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


2018 ◽  
Vol 77 (9) ◽  
pp. 1345-1353 ◽  
Author(s):  
Azita Sohrabian ◽  
Linda Mathsson-Alm ◽  
Monika Hansson ◽  
Ann Knight ◽  
Jörgen Lysholm ◽  
...  

IntroductionIndividual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.MethodsWe have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.ResultsThe majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.ConclusionsOur data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.


2020 ◽  
Vol 17 (6) ◽  
pp. 445-457
Author(s):  
Sudipta Chatterjee ◽  
Dipanjan Bhattcharjee ◽  
Sanchaita Misra ◽  
Ayindrila Saha ◽  
Nitai Pada Bhattacharyya ◽  
...  

Aim: This study investigated deregulation of lncRNAs MEG3, MALAT1, NEAT1 and their associations with clinical parameters in rheumatoid arthritis (RA). Materials & methods: LncRNAs MALAT1, MEG3, NEAT1 were quantified from peripheral blood mono-nuclear cells (PBMCs) and plasma of 82 RA patients with 15 matched controls and from knee fluid of 24 RA patients with ten osteoarthritis controls. Multivariate analyses were performed among lncRNAs and clinical parameters of RA. Results: MALAT1, MEG3, NEAT1 were increased in PBMCs, plasma, synovial fluid (p < 0.05) of RA patients. Significant correlations were observed for MEG3 with TJC (r = 0.29), NEAT1 with TJC (r = 0.49), swollen joint count (r = 0.20), DAS28-CRP (r = 0.29). Multivariate analysis revealed that 48.5% of TJC and 31.5% of swollen joint count could be predicted by lncRNAs. Conclusion: The findings suggested that the lncRNAs might be explored as probable markers in monitoring disease activity.


2008 ◽  
Vol 10 (6) ◽  
pp. R135 ◽  
Author(s):  
Francesco Ria ◽  
Romina Penitente ◽  
Maria De Santis ◽  
Chiara Nicolò ◽  
Gabriele Di Sante ◽  
...  

2020 ◽  
Vol 29 (3) ◽  
pp. 47-51
Author(s):  
Dalia A. Elsayed ◽  
Samy E. Egila ◽  
Yaser A. Abd El-Hammed ◽  
Rasha A. Elsayed ◽  
Noha Hosni Ibrahim

inflammatory autoimmune disease with a frequency of 0.5–1.0% between the adult population of developed countries. It is marked by chronic inflammation of synovial tissue and accompianed by damage of the articular cartilage and adjecent bone, leading to substantial disability. Objectives: The aim of this study is to determine serum and synovial fluid levels of calprotectin in rheumatoid arthritis patients and to determine its relation with disease activity and severity. Methodology: This study was carried out on 40 rheumatoid arthritis patients who were admitted to Rheumatology, Rehabilitation and Physical Medicine Outpatient’ clinic and Inpatient Department of Benha University Hospital .Also Thirty age and sex matched( 28 females and 2 males ) apparently healthy volunteers were included in the study as a control group . All patients were assessed by full medical history, clinical examination, functional assessment, laboratory investigations including CBC, ESR ,CRP, liver functions, RF, Anticcp antibody, and Xrays were done to both hands. Serum and synovial levels of calprotectien were measured using the ELISA technique. Results: Serum levels of calprotectien were significantly higher in RA patients than healthy subjects [p<0.001], also there was a highly statistically significant increase in the mean synovial fluid calprotectin levels than mean serum calprotectien levels [p<0.001]. Local and systemic levels of calprotectin correlate with clinical, immunological and instrumental assessments of disease activity and the inflammatory degree of the joint. Conclusion: Calprotectin could be used as a new biomarker for monitoring the disease activity and severity of RA. Larger sets are needed to confirm the diagnostic and prognostic accuracy of calprotectin in RA


2009 ◽  
Vol 28 (3) ◽  
pp. 166-171 ◽  
Author(s):  
Zoran Mijušković ◽  
Ljiljana Rackov ◽  
Janko Pejović ◽  
Sandra Živanović ◽  
Jelica Stojanović ◽  
...  

Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis PatientsRheumatoid arthritis (RA) is predominantly an intraarticular inflammatory and autoimmune disease that involves different autoantibodies and effector mechanisms. The aim of the study was to determine the utility of Circulating Immune Complexes (CIC) and complement components (C3c, C4) as possible markers for the disease activity in laboratory diagnostics. In a cross-section study 59 patients, according to the clinical criteria, were categorized into two groups: group with moderate (MA, n=24), and group with severe activity (SA, n=35) of RA. The concentration of CIC, C3c and C4 in sera (S) and synovial fluids (SF) was examined by an immunonephelometric method in both groups and compared with values in the control group (n=15) of patients with lesions of the menisci. Obtained results showed that there was no statistical significance in the values of C3c and C4, in both biological fluids, among all tested groups. Significant differences were found in the levels of CIC in both fluids, while testing the parameters (× ± SD, IU/mL) in the sera of groups with SA and MA of RA: 7.43 ± 13.40; 3.01 ± 2.92 (p<0.05) and SF: 13.47 ± 21.1, 5.33 ± 7.53 (p<0.001), respectively. These differences were higher between the group with SA and CG. Results for the concentrations of CIC were significantly higher in SF compared to sera: in the RA group with SA by 77% and group with MA by about 82%. These data could provide a confirmation of the hypothesis about local, intraarticular autoantibodies and subsequent CIC production. It can be concluded that the examination of CIC concentration in serum, and where it is possible in SF, is a useful marker of disease activity in RA patients, in contrast to the tested components of the complement. This statement does not exclude their consumption within immune effector mechanisms, but elicits the possibility that lower molecular fragments (C3d, C4d), as well as the novel activation products, could be better disease activity markers in RA patients.


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