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

Soluble Receptor for Advanced Glycation Endproducts Is Decreased in Patients with Juvenile Idiopathic Arthritis (ERA Category) and Inversely Correlates with Disease Activity and S100A12 Levels

2011 ◽  
Vol 38 (9) ◽  
pp. 1994-1999 ◽  
Author(s):  
ARPITA MYLES ◽  
VISHAD VISWANATH ◽  
YOGESH PREET SINGH ◽  
AMITA AGGARWAL
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Advanced Glycation Endproducts ◽  
Tender Joint Count ◽  
Healthy Controls ◽  
Advanced Glycation ◽  
Tender Joint ◽  
Glycation Endproducts ◽  
Paired Samples ◽  
Soluble Rage

Objective.Membrane-bound receptor for advanced glycation endproducts (mRAGE) is overexpressed in response to increasing concentrations of its ligand (e.g., S100A12) and triggers an inflammatory immune response. In contrast, soluble RAGE (sRAGE) acts as a decoy receptor and downmodulates inflammation. Decreased sRAGE levels are associated with autoimmune diseases; however, limited data are available in juvenile idiopathic arthritis (JIA). We studied sRAGE levels in patients with JIA [enthesitis-related arthritis (ERA) category].Methods.sRAGE levels were estimated in the serum of patients with ERA JIA (n = 101), systemic-onset JIA and polyarticular JIA (n = 10 each), and healthy controls (n = 45). Synovial fluid (SF) sRAGE was measured in patients with ERA, rheumatoid arthritis, reactive arthritis, and osteoarthritis (n = 10). Levels of S100A12 were also measured. Twenty-four patients with ERA were followed for 4 months. Disease activity was assessed by swollen joint count (SJC), tender joint count (TJC), and erythrocyte sedimentation rate (ESR). All levels are expressed as median (range).Results.The serum sRAGE (pg/ml) level was significantly lower in patients compared to healthy controls [515 (64–1887) vs 1542 (627–3159); p < 0.0001]. In paired samples, SF had lower levels compared to corresponding plasma level [102 (51–799) vs 481 (134–1006); p < 0.0001]. The level of S100A12 (ng/ml) was higher in SF (1042; 573–1415) than serum (638; 208–779). Serum sRAGE correlated negatively with S100A12 levels (r = −0.474; p < 0.01.), ESR (r = −0.306; p < 0.01), and SJC (r = −0.237; p < 0.05), but not with TJC (r = −0.134; p = NS). The levels of sRAGE remained stable over time in patients with stable disease.Conclusion.Levels of sRAGE are reduced in patients with ERA and correlate negatively with disease activity and S100A12 levels. sRAGE may be a modulator of inflammation in these patients.

scholarly journals Using peripheral blood immune signatures to stratify patients with adult and juvenile inflammatory myopathies

Rheumatology ◽  
2019 ◽  
Author(s):  
Meredyth G Ll Wilkinson ◽  
Anna Radziszewska ◽  
Chris Wincup ◽  
Yiannis Ioannou ◽  
David A Isenberg ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Assessment Tool ◽  
Immune Cell ◽  
Memory B Cells ◽  
Healthy Controls ◽  
Immune Signatures

AbstractObjectiveThe inflammatory idiopathic myopathies (IIM) are a group of rare autoimmune diseases defined by muscle weakness and characterized by pro-inflammatory infiltrates in muscle. Little is known about the immunological profile in peripheral blood of these patients and how this relates to IIM subtypes. This study aimed to stratify adult and juvenile-onset IIM patients according to immune cell profile.MethodsPeripheral blood mononuclear cells from 44 patients with adult myositis (AM), 15 adolescent-onset juvenile dermatomyositis (a-JDM), and 40 age-matched healthy controls were analysed by flow cytometry to quantify 33 immune cell subsets. Adult myositis patients were grouped according to myositis subtype; DM and polymyositis; and also autoantibody specificity. Disease activity was determined by the myositis disease activity assessment tool and clinicians’ decision on treatment.ResultsUnique immune signatures were identified for DM, polymyositis and a-JDM compared with healthy controls. DM patients had a T-cell signature comprising increased CD4+ and TH17 cell frequencies and increased immune cell expression of IL-6. Polymyositis patients had a B-cell signature with reduced memory B cells. A-JDM had decreased naïve B cells and increased CD4+T cells. All patient groups had decreased CD8+central memory T-cell frequencies. The distinct immune signatures were also seen when adult myositis patients were stratified according to auto-antibody expression; patients with anti-synthetase-antibodies had reduced memory B cells and patients with autoimmune rheumatic disease overlap had an elevated Th17 profile.ConclusionUnique immune signatures were associated with adult vs juvenile disease. The Th17 signature in DM patients supports the potential use of IL-17 inhibitors in treatment of IIMs.

scholarly journals IL-36γ in Enthesitis related Juvenile Idiopathic Arthritis and its association with disease activity.

2021 ◽  
Author(s):  
Sanjukta Majumder et al.
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Feedback Loop ◽  
Mononuclear Cells ◽  
Inflammatory Bowel ◽  
Fibroblast Like Synoviocytes ◽  
Pro Inflammatory Cytokines

IL-36 has been implicated in the pathogenesis of spondyloarthropathies (SpA) like psoriasis and inflammatory bowel disease. Enthesitis related arthritis (ERA) category of juvenile idiopathic arthritis is a form of juvenile SpA, however no data is available on the role of IL-36 in this disease. IL-36α, β, γ and IL-36R mRNA expression in blood and synovial fluid mononuclear cells and IL-36α, γ, IL-36Ra, IL-6 and IL-17 levels were measured in serum and synovial fluid (SF). IL-36γ production by fibroblast like synoviocytes (FLS) by pro-inflammatory cytokines and its effect on FLS was also studied.mRNA levels of IL-36α, IL-36γ and IL-36R were increased in PBMCs of ERA patients as compared to healthy controls however only IL-36γ was measurable in serum of one third of patients. In SFMCs, all 4 mRNA were detectable but were lower than RA patients. SF IL-36γ levels correlated with disease activity score (r=0.51, p< 0.0001), SF IL-6 (r=0.4,p= 0.0063) and IL-17 levels (r=0.57,p=0.0018). Pro-inflammatory cytokines increased expression of IL-36γ and IL-6 in FLS cultures. SFs from 5 ERA patients also increased expressions of IL-36γ and IL-6 in FLS which could be blocked by using IL-36Ra.This suggests that pro-inflammatory cytokines aid in upregulation of IL-36γ which in turn upregulates expression of IL-6. This might lead to a positive feedback loop of inflammation in ERA. Association of SF levels of IL-36γ with disease activity further supports this possibility. IL-36Ra based therapy may have a role in ERA.

scholarly journals Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Kawaljit Kaur ◽  
Shahram Vaziri ◽  
Marcela Romero-Reyes ◽  
Avina Paranjpe ◽  
Anahid Jewett
Keyword(s):  
Periodontal Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Oral Disease ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of 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 The immunoregulatory function of peripheral blood CD71+ erythroid cells in systemic-onset juvenile idiopathic arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hikaru Kanemasa ◽  
Masataka Ishimura ◽  
Katsuhide Eguchi ◽  
Tamami Tanaka ◽  
Etsuro Nanishi ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Active Phase ◽  
Serum Levels ◽  
Cell Interaction ◽  
Erythroid Cells ◽  
Peripheral Blood Mononuclear ◽  
Systemic Onset

AbstractCD71+ erythroid cells (CECs) are recognized to have an immunoregulatory function via direct cell–cell interaction and soluble mediators. Circulating CECs appear in newborns or patients with hemolytic and cardiopulmonary disorders. To assess the biological role of CECs in systemic inflammation, we studied the gene expression and function in systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells of SoJIA patients expressed upregulated erythropoiesis-related genes. It represented the largest expansion of CECs during active phase SoJIA among other inflammatory diseases. Despite the opposing roles of erythropoietin and hepcidin in erythropoiesis, both serum levels were in concert with the amounts of SoJIA-driven CECs. Circulating CECs counts in inflammatory diseases were positively correlated with the levels of C-reactive protein, IL-6, IL-18, or soluble TNF receptors. Co-culture with active SoJIA-driven CECs suppressed secretions of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top upregulated gene in SoJIA-driven CECs was ARG2 compared with CECs from cord blood controls, although cytokine production from monocytes was suppressed by co-culture, even with an arginase inhibitor. CECs are driven to the periphery during the acute phase of SoJIA at higher levels than other inflammatory diseases. Circulating CECs may control excessive inflammation via the immunoregulatory pathways, partly involving arginase-2.

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