scholarly journals Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis

2008 ◽  
Vol 56 (4) ◽  
pp. 283-289 ◽  
Author(s):  
Elżbieta Smolewska ◽  
Barbara Cebula ◽  
Henryka Brózik ◽  
Jerzy Stańczyk
Keyword(s):  
Dendritic Cells ◽  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Peripheral Blood

Th1 and Th17 Predominance in the Enthesitis-related Arthritis Form of Juvenile Idiopathic Arthritis

2009 ◽  
Vol 36 (8) ◽  
pp. 1730-1736 ◽  
Author(s):  
ANKIT MAHENDRA ◽  
RAMNATH MISRA ◽  
AMITA AGGARWAL
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Health Assessment ◽  
Treg Cells ◽  
Th2 Cells ◽  
Median Frequency ◽  
Enthesitis Related Arthritis

Objective.A Th1 biased immune response in synovial fluid has been reported in children with polyarticular and extended oligoarticular-type juvenile idiopathic arthritis (JIA). We investigated T cell phenotypes including Th1, Th2, Th17, and Treg with emphasis on Th17 and Treg, in order to differentiate cytokines in the enthesitis-related arthritis (ERA) form of JIA.Methods.The frequencies of Th1, Th2, Th17, and Treg cells were determined by flow cytometry in peripheral blood (PB) and synovial fluid from patients with ERA and healthy subjects. Levels of interleukin 1ß (IL-1ß), IL-6, IL-21, IL-23, and transforming growth factor ß (TGF-ß), cytokines that influence Th17 lineage cells, were measured in paired plasma and synovial fluid (SF) samples by ELISA. Frequencies are expressed as percentages and cytokine levels as pg/ml.Results.There were no differences in blood samples in the frequency of Th1, Th2, Th17, and Treg cells between patients and controls. In paired samples, the median frequency of CD4+IFN-γ+ (20.49 vs 4.03; p < 0.005) and CD4+IL-17+ (2.27 vs 0.57; p < 0.01) cells was significantly higher in SF compared to PB, respectively; whereas the frequency of CD4+IL-4+ (1.79 vs 2.29; p < 0.04) cells was significantly reduced in the SF compared to PB. There was no difference in the frequency of regulatory T cells. Patients receiving methotrexate had fewer Th2 cells, whereas the Childhood Health Assessment Questionnaire score had a negative association with the frequency of Treg. Median levels of IL-1ß (p < 0.008), IL-6 (p < 0.0001), and IL-17 (p < 0.0001) were higher in SF than in plasma and levels of TGF-ß were lower (p < 0.001). Levels of IL-21 were similar in SF and plasma, whereas IL-23 was undetectable.Conclusion.In patients with ERA, peripheral blood Th1, Th2, Th17, and Treg cells were unchanged, but Th1 and Th17 cells were increased and Th2 cells were reduced in the SF compared to blood. Elevated IL-1ß and IL-6 in SF may be responsible for increased Th17 cells.

scholarly journals Imbalance of Th17 and T-regulatory cells in peripheral blood and synovial fluid in treatment naïve children with juvenile idiopathic arthritis

2014 ◽  
Vol 1 ◽  
pp. 71-76 ◽  
Author(s):  
Joanna Szymańska-Kałuża ◽  
Barbara Cebula-Obrzut ◽  
Piotr Smolewski ◽  
Jerzy Stanczyk ◽  
Elżbieta Smolewska
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Regulatory Cells ◽  
Treatment Naïve

Regulation of peripheral blood and synovial fluid lymphocyte apoptosis in juvenile idiopathic arthritis

2004 ◽  
Vol 33 (1) ◽  
pp. 7-12 ◽  
Author(s):  
E Smolewska ◽  
H Brózik ◽  
P Smolewski ◽  
Z Darzynkiewicz ◽  
J Stańczyk
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Peripheral Blood ◽  
Lymphocyte Apoptosis

scholarly journals AB0018 ACCUMULATION OF FUNCTIONALLY MATURE CD1C+ DENDRITIC CELLS CONTRIBUTES TO SYNOVIAL INFLAMMATION IN INFLAMMATORY ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1043.2-1043
Author(s):  
M. Canavan ◽  
V. Marzaioli ◽  
V. Bhargava ◽  
S. Nagpal ◽  
P. Gallagher ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Synovial Fluid ◽  
Research And Development ◽  
Rna Sequencing ◽  
Synovial Tissue ◽  
Peripheral Blood ◽  
Synovial Inflammation ◽  
Research Support

Background:Myeloid Dendritic Cells (DC) are potent antigen presenting cells that can be subdivided into CD141 and CD1c+ DC. We have previously reported an unacknowledged role for CD141+DC in the IA synovium. However, the identification and function of CD1c+ DC in the IA synovium has yet to be fully elucidated.Objectives:To investigate if CD1c+DC reside in the IA synovium and ascertain if they represent a unique population, distinct from peripheral CD1c+DC and if they contribute to synovial inflammation.Methods:Synovial tissue (ST) biopsies and synovial fluid mononuclear cells (SFMC) were obtained via arthroscopy and healthy control (HC) ST was obtained during ACL surgery. Synovial tissue single cells suspensions were generated following enzymatic and mechanical digestion. Single cell analysis of synovial tissue cell suspensions, along with PBMC and SFMC was performed by multicolour flow cytometry. CD1c+DC were sorted from IA synovial fluid and peripheral blood and bulk RNA sequencing was performed. CD1c+DC functionality and maturation was assessed using OVA DQ phagocytosis assays, multiplex ELISA and DC: T cell cocultures.Results:Within the circulation the frequency of CD1c+DC are significantly decreased in IA peripheral blood compared to HC (p<0.01) in addition to expressing significantly higher levels of the maturation markers CD80 (p<0.01) and CD40 (p=0.08). IA peripheral blood DC also express significantly higher levels of CXCR3 (p<0.01) and CCR7 (p<0.05) compared to HC - suggestive of DC migration from the periphery to the synovium. Following RNA-seq analysis, IPA and differentially expressed gene (DEG) analysis revealed an enrichment in genes involved in DC maturation, TLR signalling and chemokine signalling in IA peripheral blood compared to HC. In support of the hypothesis that DC migrate and accumulate in the IA synovium, CD1c+ DC were identified in IA ST and were significantly enriched compared to IA peripheral blood (p<0.01). IA ST CD1c+DC express significantly higher levels of the activation marker CD80 compared to IA peripheral blood (p<0.05) or HC ST (p<0.05). Upon examination of IA synovial fluid, we report similar findings to ST, whereby CD1c+DC are enriched in synovial fluid compared to PB (p<0.001). Moreover, RNA sequencing and PCA analysis of synovial versus blood CD1c+DC revealed distinct transcriptional variation between both sites. Functionally, synovial CD1c+DC express higher levels of the maturation markers CD80, CD83, CD40, PD-L1 and BTLA (all p<0.05) and have distinct coexpression of these maturation markers which is unique to the synovium. Synovial CD1c+DC are less phagocytic compared to peripheral blood DC, have decreased production of MMP1 and MMP9 and importantly are still capable of additional activation in-vitro. Finally, synovial CD1c+DC induce the proinflammatory cytokines TNFα, GMCSF, IL-17a and IFNγ from CD4+ T-cells in allogeneic DC: T cells cocultures.Conclusion:Mature circulatory CD1c+DC migrate and accumulate in the IA synovium. Synovial DC are present in the IA synovium in a mature state, have distinct tissue specific characteristics and can induce proinflammatory CD4+T cell responses.Acknowledgements:We would like to thank all the patients who contributed to this studyDisclosure of Interests:Mary Canavan: None declared, Viviana Marzaioli: None declared, Vipul Bhargava Employee of: Janssen Research and Development, Sunil Nagpal Employee of: Janssen Research and Development, Phil Gallagher: None declared, Conor Hurson: None declared, Ronan Mullan: None declared, Douglas Veale Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, MSD, UCB, Consultant of: Abbvie, Janssen, Novartis, Pfizer, MSD, UCB, Grant/research support from: Pfizer, Janssen, AbbVie, UCB, Ursula Fearon Speakers bureau: Abbvie, Grant/research support from: Pfizer, Janssen, Abbvie, UCB

scholarly journals FRI0451 RELATIONSHIP BETWEEN MEMBRANE-BOUND AND SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS AND DISEASE ACTIVITY IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 823.3-823
Author(s):  
D. Clemente ◽  
A. García-Salido ◽  
G. Melen ◽  
M. Ramirez-Orellana ◽  
J. C. López Robledillo
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Advanced Glycation Endproducts ◽  
Healthy Controls ◽  
Advanced Glycation ◽  
Membrane Bound ◽  
Rage Expression

Background:Membrane-bound receptor for advanced glycation endproducts (mRAGE) expression increases in the presence of its ligands (e.g., High Mobility Group Box 1, HMGB1) and triggers an inflammatory immune response. In contrast, soluble RAGE (sRAGE) acts as a decoy receptor and downmodulates inflammation. Some studies have demonstrated that decreased sRAGE levels are negatively correlated with disease activity in juvenile idiopathic arthritis (JIA) but expression of mRAGE has not been studied.Objectives:The aim of this study is to evaluate mRAGE and sRAGE on peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MC) of patients with JIA and healthy controls and to assess whether there is an association with established inflammatory markers and clinical measures.Methods:Matching samples of blood and synovial fluid were collected from patients with JIA (n=33) with active arthritis. RAGE expression on mononuclear cells was analyzed using flow cytometry. The intensity of RAGE expression was measured as mean fluorescence intensity (MFI). Levels of sRAGE and HMGB1 were determined with a specific ELISA kit in the serum and synovial fluid (SF) of patients with JIA. Relation between cellular RAGE and sRAGE with disease activity parameters [JADAS71, CHAQ, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] and HMGB1 were described. We compare mRAGE expression in PBMC and serum sRAGE levels between JIA patients and age-matched healthy controls (n=43).Results:24 patients with oligoarticular JIA and 9 patients with poliarticular JIA were studied, 8/23 females with a mean age of 7,7 ± 3,6. MFI of mRAGE in PBMC and SFMC of JIA patients were significantly decreased in comparison with MFI of mRAGE in PBMC of healthy controls. Although serum levels of sRAGE were not different between patients and controls, sRAGE levels were lower in SF (570.2 [458.5- 773.0]) compared to PB (759.7 [628.6-890.3]) in JIA patients, especially in the poliarticular group. By contrast, HMGB1 levels in SF were significantly higher than in PB of JIA patients. MFI of mRAGE in PBMC was correlated with JADAS71 (p 0.01) and CHAQ (p 0.07). There were no significant correlations between serum sRAGE and HMGB1 with JADAS71, CHAQ, CRP and ESR.Conclusion:The sRAGE/RAGE system may be a modulator of inflammation in JIA patients. Differences between levels of sRAGE and HMGB1 in synovial fluid versus peripheral blood in patients with JIA may suggest a local role in the pathogenesis of JIA.JIA patients (n=33)Healthy controls (n=43)Age (years)7,7 ± 3,67,9 ± 4,7 SDSex (boys/girls)9/2430/13JIA category Oligoarticular24 Poliarticular9Treatment NSAIDs20 MTX12 ANTI-TNFα1ESR (mm/h)26.3 (4-78)CRP (mg/dL)1.4 (0,5-6,5)CHAQ0.375 (0-2.375)JADAS-718.1 (2.8-16.3)Disclosure of Interests:Daniel Clemente Paid instructor for: Novartis, Speakers bureau: Novartis, Abvie, Roche, Sobi, Alberto García-Salido: None declared, Gustavo Melen: None declared, Manuel Ramirez-Orellana: None declared, J.C. López Robledillo: None declared

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