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 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

Thrombin-cleaved Osteopontin Is Increased in Urine of Patients with Rheumatoid Arthritis

2010 ◽  
Vol 37 (4) ◽  
pp. 704-710 ◽  
Author(s):  
KIORI SHIO ◽  
HIROKO KOBAYASHI ◽  
TOMOYUKI ASANO ◽  
RIE SAITO ◽  
HARUYO IWADATE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Tender Joint Count ◽  
Healthy Controls ◽  
C Reactive Protein ◽  
Tender Joint ◽  
Matrix Metalloproteinase 3 ◽  
Reactive Protein ◽  
Urine Levels

Objective.To measure concentrations of the thrombin-cleaved isoform of osteopontin (OPN) in urine and plasma of patients with rheumatoid arthritis (RA), and to assess whether levels of thrombin-cleaved OPN are associated with measures of RA.Methods.Subjects comprised 70 patients with RA, 20 patients with osteoarthritis (OA), and 46 healthy controls. RA disease activity was evaluated by tender joint count, swollen joint count, patient’s global assessment of disease activity, erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF), as well as 28-joint count Disease Activity Score (DAS28). OPN levels in plasma and urine were measured by ELISA.Results.Median levels of thrombin-cleaved OPN in urine (U-half) were significantly higher in RA patients (143.5 pmol/mmol Cr) than in healthy controls (67.9 pmol/mmol Cr) or OA patients (69.8 pmol/mmol Cr). Thrombin-cleaved OPN was not detected in plasma. U-half levels correlated significantly with levels of CRP (r = 0.26, p = 0.03), ESR (r = 0.26, p = 0.03), and RF (r = 0.28, p = 0.03). Median U-half levels were significantly higher in patients with stage III (249.9 pmol/mmol Cr) and IV (251.6 pmol/mmol Cr) disease than in patients with stage I (98.6 pmol/mmol Cr) disease.Conclusion.Our results suggest that urine levels of the thrombin-cleaved isoform of OPN may reflect the severity of active inflammatory arthritis in patients with RA.

scholarly journals AB0174 FATIGUE IN RHEUMATOID ARTHRITIS: A CASE-CONTROL STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1113.2-1113
Author(s):  
A. Fazaa ◽  
H. Boussaa ◽  
K. Ouenniche ◽  
S. Miladi ◽  
M. Sellami ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Demographic Data ◽  
Tender Joint Count ◽  
P Value ◽  
Common Symptom ◽  
Healthy Controls ◽  
Tender Joint ◽  
Cross Sectional ◽  
The Mean

Background:Fatigue is a common symptom in many chronic inflammatory diseases, including rheumatoid arthritis (RA). It is considered one of the most frustrating, uncontrollable, and overwhelming symptoms. However, most of rheumatologists do not assess fatigue despite its clinical significance and its impact on patients’ lives.Objectives:The aims of this study were to determine whether RA patients express more fatigue than healthy controls, and to analyze its correlation with disease activity.Methods:We conducted a cross-sectional study including patients with RA (ACR/EULAR 2010) and healthy controls matched for sex and age. Patients with other acute or chronic diseases that may induce fatigue (such as cancer, infection or depression) were excluded. Demographic data and the following clinical parameters were collected: pain Visual Analog Scale (VAS), Global Patient Assessment (GPA), tender joint count (TJC) and swollen joint count (SJC), Erythrocyte Sedimentation Rate (ESR), C Protein Reactive (CRP), Disease Activity Score 28 (DAS28), and Health Assessment Questionnaire (HAQ). Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) which is a short 13-item questionnaire validated in RA. The score FACIT-F ranges between 0 and 52. Fatigue was considered mild if the FACIT-F score was ≥40, moderate if 20≤FACIT-F<40 and severe if 0≤FACIT-F<20. A p value inferior to 0.05 was considered significant.Results:We included 100 RA patients (84 women and 16 men) with a mean age of 49.5±10 years old [18-65]. The mean disease duration was 87.3 months [1-360]. The mean pain VAS was 49 cm [0-100] and the mean GPA was 47.8 cm [0-100]. The mean TJC and SJC were 5.3 [0-36] and 1 [0-9] respectively. The mean levels of ESR and CRP were 38.1 mm [10-120] and 10.8 mg/l [2-61] respectively. The mean DAS28 ESR was 3.68 [1.90-8.33] and the mean HAQ score was 0.90 [0-2.75].Thirty-nine healthy controls were enrolled including 35 women and 4 men with a mean age of 51.2 years old [30-64].The mean FACIT-F score was 27.1 [0-51] in RA patients versus 46.2 [0-52] in healthy controls (p<0.001). Among RA patients, 57% had moderate fatigue and 26% had severe fatigue.A significant negative correlation was noted between the FACIT-F score and the following parameters in RA patients: TJC (r=-0.568, p<0.001), SJC (r=-0.274, p<0.001), pain VAS (r=-0.605, p<0.001), GPA (r=-0.658, p<0.001), ESR (r=-0.405, p<0.001), CRP (r=-0.149, p<0.001), DAS28 (r=-0.837, p<0.001) and HAQ (r=-0.634, p<0.001).Conclusion:Fatigue was significantly more observed in RA patients. This symptom was correlated with disease activity and disability. It is important to recognize and manage fatigue in order to improve patients’ quality of life.Disclosure of Interests:None declared

scholarly journals Pseudomonas aeruginosa significantly increases expression of receptor for advanced glycation endproducts (RAGE) in the septicemia suffering patients

2021 ◽  
Vol 11 (5) ◽  
pp. 984-988
Author(s):  
A. Kariminik ◽  
F. Hosseini ◽  
E. Nasiri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Immune Responses ◽  
Advanced Glycation Endproducts ◽  
Cell Surface Receptor ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Surface Receptor ◽  
A Cell

Receptor for Advanced Glycation Endproducts (RAGE) is a cell surface receptor, which recognizes several endogenous and exogenous molecules and subsequently induces expression of several molecules including chemokines. Chemokines are members of the cytokine superfamily and participate in several immune system functions, including cell migration, inflammation, angiogenesis/angiostasis etc. CXC ligand 11 (CXCL11) is an important chemokine which participates in the induction of appropriate immune responses against microbes, including bacteria. The main mechanisms responsible to overcome septicemia are yet to be clarified. Thus, it has been hypothesized that RAGE may participate in induction of CXCL11 in response to the microbial agents. Due to the fact that immune responses play key roles in limitation of infection, it has been proposed that RAGE may inhibit spread of septicemia. Therefore, in this project mRNA levels of RAGE and CXCL11 were explored in the patients suffering from septicemia versus healthy controls. RAGE and CXCL11 expression levels in the 80 subjects, including 40 septicemia patients and 40 healthy controls were explored using Real-Time PCR technique. Accordingly, by using the specific primer against RAGE and CXCL11 in a Rotorgene vehicle the mRNA levels have been determined. The septicemia and the sources of the bacteria in the blood were diagnosed using microbial cultures. The results demonstrated that although mRNA levels for RAGE and CXCL11 did not change in the septicemia patients vs. healthy controls, mRNA levels of RAGE were significantly higher in the patients infected by Pseudomonas aeruginosa compared to those infected by other bacteria, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii. RAGE and CXCL11 mRNA levels did not differ among male and female patients. Based on the results it seems that RAGE is a critical receptor against P. aeruginosa during septicemia and more investigations, especially on the RAGE down-stream molecules can clarify its main roles against P. aeruginosa.

scholarly journals Noninvasive Measurement of Skin Autofluorescence Is Increased in Patients with Systemic Sclerosis: An Indicator of Increased Advanced Glycation Endproducts?

2012 ◽  
Vol 39 (8) ◽  
pp. 1654-1658 ◽  
Author(s):  
ANDREA K. MURRAY ◽  
TONIA L. MOORE ◽  
JOANNE B. MANNING ◽  
CHRISTOPHER E.M. GRIFFITHS ◽  
ARIANE L. HERRICK
Keyword(s):  
Oxidative Stress ◽  
Systemic Sclerosis ◽  
Upper Limb ◽  
Advanced Glycation Endproducts ◽  
Proximal Phalanx ◽  
Healthy Controls ◽  
Skin Autofluorescence ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Primary Raynaud’S Phenomenon

Objective.Skin autofluorescence noninvasively assesses expression of advanced glycation endproducts and therefore potentially the presence of oxidative stress that is implicated in the pathogenesis of systemic sclerosis (SSc). We investigated whether autofluorescence was increased in patients with SSc, primary Raynaud’s phenomenon (RP), and morphea as compared to healthy controls.Methods.Measurements of autofluorescence were made at 5 upper limb sites in 16 healthy controls, 16 patients with diffuse cutaneous SSc (dcSSc), 15 with limited cutaneous SSc (lcSSc), 15 with primary RP, and 13 with morphea. For patients with morphea, additional measurements were made at the affected and an adjacent unaffected site.Results.Autofluorescence was significantly increased in patients with dcSSc but not lcSSc as compared to controls at the proximal phalanx [dcSSc median 0.15, interquartile range (IQR) 0.10–0.24, vs control 0.10, IQR 0.07–0.13; p = 0.014], dorsum of the hand (dcSSc 0.17, IQR 0.11–0.36, vs control 0.12, IQR 0.09–0.17; p = 0.031), the wrist (dcSSc 0.22, IQR 0.13–0.33, vs control 0.13, IQR 0.09–0.18; p = 0.005), and forearm (dcSSc 0.19, IQR 0.12–0.47, vs control 0.14, IQR 0.10–0.16; p = 0.022). There was a trend for autofluorescence to be increased in patients with lcSSc and at morphea sites, compared to noninvolved skin.Conclusion.Autofluorescence is increased in patients with dcSSc compared to primary RP and to healthy controls. This suggests increased oxidative stress and the potential for autofluorescence as a biomarker.

Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

2019 ◽  
Vol 15 (4) ◽  
pp. 316-320
Author(s):  
Mir Amir Aghdashi ◽  
Seyedmostafa Seyedmardani ◽  
Sholeh Ghasemi ◽  
Zohre Khodamoradi
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Arthritis ◽  
Unknown Etiology ◽  
Tender Joint Count ◽  
Serum Samples ◽  
Tender Joint ◽  
Cross Sectional ◽  
Calprotectin Level ◽  
Remission Phase

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

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