Interleukin 1 beta in synovial fluid is related to local disease activity in rheumatoid arthritis

1990 ◽  
Vol 10 (5) ◽  
pp. 217-219 ◽  
Author(s):  
M. Rooney ◽  
J. A. Symons ◽  
G. W. Duff
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Local Disease

scholarly journals AB0108 IRAK4 INHIBITION SUPPRESSES PROINFLAMMATORY CYTOKINE PRODUCTION FROM HUMAN MACROPHAGES STIMULATED WITH SYNOVIAL FLUID FROM RHEUMATOID ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1353.2-1353
Author(s):  
A. Yadon ◽  
D. Ruelas ◽  
G. Min-Oo ◽  
J. Taylor ◽  
M. R. Warr
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Signaling Pathways ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Proinflammatory Cytokine Production ◽  
Human Macrophages ◽  
Percent Suppression

Background:Rheumatoid arthritis (RA) is characterized by chronic, uncontrolled joint inflammation and tissue destruction. Macrophages are thought to be key mediators in both the initiation and perpetuation of this pathology.1,2The RA synovium contains a complex inflammatory milieu that can stimulate macrophage-dependent production of proinflammatory cytokines through multiple signaling pathways.1,2Existing evidence indicates that toll-like receptors (TLRs) and interleukin-1 receptors (IL-1R) along with their agonists, damage-associated molecular patterns (DAMPs) and IL-1β, are highly expressed in RA joints and are important mediators of synovial macrophage activation and proinflammatory cytokine production.1-9IRAK4 (interleukin-1 receptor-associated kinase 4) is a serine/threonine kinase that facilitates TLR and IL-1R signaling in many cell types, including macrophages.10IRAK4 inhibition represents an opportunity to reduce proinflammatory cytokine production in the joints of patients with RA.Objectives:To investigate the effect of a highly selective IRAK4 inhibitor on proinflammatory cytokine production from human macrophages stimulated with synovial fluid from patients with RA.Methods:Primary human monocytes from 2 independent donors were differentiated for 6 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) to generate human monocyte-derived macrophages (hMDMs). hMDMs were then pretreated with an IRAK4 inhibitor for 1 hour and subsequently stimulated for 24 hours with RA synovial fluid from 5 patients. Culture supernatants were then assessed for secretion of proinflammatory cytokines by MesoScale Discovery.Results:RA synovial fluid stimulation of hMDMs resulted in the production of several proinflammatory cytokines, including IL-6, IL-8, and TNFα. Pretreatment of hMDMs with an IRAK4 inhibitor resulted in the dose-dependent inhibition of IL-6, IL-8, and TNFα production, with an average EC50± SD of 27 ± 31, 26 ± 41, and 28 ± 22 nM, respectively. Maximal percent suppression ± SD of IL-6, IL-8, and TNFα were 76 ± 8.8, 73 ± 15, and 77 ± 13, respectively. To evaluate the specific IRAK4-dependent signaling pathways mediating this response, hMDMs were pretreated with inhibitors of TLR4 (TAK242) and IL-1R (IL-1RA) prior to stimulation with RA synovial fluid. Both TAK242 and IL-1RA inhibited proinflammatory cytokine production. For TAK242, maximal percent suppression ± SD of IL-6, IL-8, and TNFα were 39 ± 25, 48 ± 24, and 50 ± 21, respectively. For IL-1RA maximal percent suppression ± SD of IL-6, IL-8, and TNFα were 18 ± 18, 20 ± 23, and 16 ± 18, respectively. The broad range of inhibition across each stimulation highlights the complexity and variability in the signaling pathways mediating proinflammatory cytokine production from hMDMs stimulated with RA synovial fluid, but demonstrates that RA synovial fluid can stimulate proinflammatory cytokine production in hMDMs, at least partly, through IRAK4-dependent pathways.Conclusion:This work demonstrates that IRAK4 inhibition can suppress proinflammatory cytokine production from macrophages stimulated with synovial fluid from patients with RA and supports a potential pathophysiological role for IRAK4 in perpetuating chronic inflammation in RA.References:[1]Smolen JS, et al.Nat Rev Dis Primers.2018;4:18001.[2]Udalova IA, et al.Nat Rev Rheumatol.2016;12(8):472-485.[3]Joosten LAB, et al.Nat Rev Rheumatol.2016;12(6):344-357.[4]Huang QQ, Pope RM.Curr Rheumatol Rep.2009;11(5):357-364.[5]Roh JS, Sohn DH.Immune Netw.2018;18(4):e27.[6]Sacre SM, et al.Am J Pathol.2007;170(2):518-525.[7]Ultaigh SNA, et al.Arthritis Res Ther.2011;13(1):R33.[8]Bottini N, Firestein GS.Nat Rev Rheumatol.2013;9(1):24-33.[9]Firestein GS, McInnes IB.Immunity.2017;46(2):183-196.[10]Janssens S, Beyaert R.Mol Cell.2003;11(2):293-302.Disclosure of Interests:Adam Yadon Employee of: Gilead, Debbie Ruelas Employee of: Gilead, Gundula Min-Oo Employee of: Gilead, James Taylor Employee of: Gilead, Matthew R. Warr Employee of: Gilead

scholarly journals POS0578 CORRELATION BETWEEN EXPRESSION LEVELS OF MIR-155 AND MIR-223 IN SYNOVIAL FLUID AND ULTRASOUND SCORES FOR ACTIVE SYNOVITIS IN RHEUMATOID ARTHRITIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 522.3-523
Author(s):  
R. Shumnalieva ◽  
D. Kachakova ◽  
R. Kaneva ◽  
Z. Kolarov ◽  
S. Monov
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Clinical Practice ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Power Doppler ◽  
Joint Inflammation ◽  
Expression Levels ◽  
Ultrasound Features ◽  
Local Expression

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

scholarly journals Histamine index and clinical expression of rheumatoid arthritis activity

2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Joint Destruction ◽  
Clinical Expression ◽  
Histamine Concentration ◽  
Significant Difference ◽  
Rheumatoid Arthritis Activity

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.

scholarly journals Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis

2018 ◽  
Vol 77 (9) ◽  
pp. 1345-1353 ◽  
Author(s):  
Azita Sohrabian ◽  
Linda Mathsson-Alm ◽  
Monika Hansson ◽  
Ann Knight ◽  
Jörgen Lysholm ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Immune Complexes ◽  
Magnetic Beads ◽  
Joint Destruction ◽  
Joint Pathology ◽  
A New Technique ◽  
Laboratory Measures

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.

Increase in MEG3, MALAT1, NEAT1 significantly predicts the clinical parameters in patients with rheumatoid arthritis

2020 ◽  
Vol 17 (6) ◽  
pp. 445-457
Author(s):  
Sudipta Chatterjee ◽  
Dipanjan Bhattcharjee ◽  
Sanchaita Misra ◽  
Ayindrila Saha ◽  
Nitai Pada Bhattacharyya ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Multivariate Analysis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Multivariate Analyses ◽  
Clinical Parameters

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.

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