Synovial fluid RANKL and matrix metalloproteinase levels in enthesitis related arthritis subtype of juvenile idiopathic arthritis

2008 ◽  
Vol 29 (8) ◽  
pp. 907-911 ◽  
Author(s):  
Shilpi Agarwal ◽  
Ramnath Misra ◽  
Amita Aggarwal
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Matrix Metalloproteinase ◽  
Enthesitis Related Arthritis

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.

Levels of Serum Matrix Metalloproteinase-3 Correlate with Disease Activity in the Enthesitis-related Arthritis Category of Juvenile Idiopathic Arthritis

2011 ◽  
Vol 38 (11) ◽  
pp. 2482-2487 ◽  
Author(s):  
VISHAD VISWANATH ◽  
ARPITA MYLES ◽  
RAJESHWAR DAYAL ◽  
AMITA AGGARWAL
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Matrix Metalloproteinase ◽  
Disease Activity ◽  
Global Assessment ◽  
Tender Joint Count ◽  
Matrix Metalloproteinase 3 ◽  
Enthesitis Related Arthritis ◽  
Activity Measures ◽  
Global Disease Activity ◽  
Disease Activity Measures

Objective.Serum matrix metalloproteinase-3 (MMP-3) has been shown to reflect disease activity in ankylosing spondylitis (AS) and rheumatoid arthritis. Elevated levels have been found in juvenile idiopathic arthritis (JIA). In the enthesitis-related arthritis category of JIA (JIA-ERA), we studied whether serum MMP-3 levels and ratios of MMP-3/tissue inhibitor of metalloproteinase (TIMP-1) are correlated with disease activity and whether they are sensitive to change in disease activity.Methods.A total of 54 patients with JIA-ERA (International League of Associations for Rheumatology criteria) were enrolled for study. Baseline disease activity measures included tender and swollen joint counts, Maastricht AS Enthesitis Score, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), patient assessment of pain and global disease activity, physician assessment of global disease activity, and erythrocyte sedimentation rate (ESR). Serum MMP-3 and TIMP-1 levels were measured using ELISA. A group of 24 patients were followed up for longitudinal study.Results.The mean age of 54 patients (48 males) at disease onset was 11.8 ± 4.19 years and duration of disease was 5.2 ± 4.3 years. Median ESR was 65 mm/h (range 46.5–97) and median BASDAI was 3.4 (range 2.5–4.7). Median MMP-3, TIMP-1, and MMP-3/TIMP-1 ratio were 50.4 ng/ml (IQR 13.0–193.8), 228.9 ng/ml (IQR 108.2–290.4), and 0.3 (IQR 0.07–1.13), respectively. At inclusion MMP-3 levels correlated directly with various disease activity measures: tender joint count (TJC; r = 0.60), swollen joint count (SJC; r = 0.45), BASFI (r = 0.29), BASDAI (r = 0.32), ESR (r = 0.49), physician global assessment (r = 0.40), patient visual analog scale for pain (r = 0.28), and patient global assessment (r = 0.38; all p < 0.05). MMP-3/TIMP-1 ratio correlated only with TJC (r = 0.51), SJC (r = 0.39), and ESR (r = 0.34; p < 0.05). At followup, change in MMP-3 correlated with changes in TJC (r = 0.42) and SJC (r = 0.44; p < 0.05), while change in ESR did not correlate with change in any disease activity measure.Conclusion.MMP-3 levels are a good marker for disease activity in JIA-ERA.

scholarly journals Cross-sectional and Longitudinal Evaluation of Bone Mass in Children and Young Adults with Juvenile Idiopathic Arthritis: The Role of Bone Mass Determinants in a Large Cohort of Patients

2010 ◽  
Vol 37 (9) ◽  
pp. 1935-1943 ◽  
Author(s):  
STEFANO STAGI ◽  
LAURA MASI ◽  
SERENA CAPANNINI ◽  
ROLANDO CIMAZ ◽  
GIULIA TONINI ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Bone Mass ◽  
Bone Mineral ◽  
Large Cohort ◽  
Close Monitoring ◽  
Mineral Density ◽  
Cross Sectional ◽  
Bone Mineral Apparent Density ◽  
Longitudinal Evaluation ◽  
Enthesitis Related Arthritis

Objective.To assess the prevalence of reduced spine bone mineral apparent density (BMAD), and to identify the main predictors of reduced spine BMAD in a cross-sectional and longitudinal evaluation of the same large cohort of patients with juvenile idiopathic arthritis (JIA). There are few prospective data on bone mass evaluation in a large number of patients with JIA, and with enthesitis-related arthritis onset.Methods.Two hundred nineteen patients with JIA (median age 8.7 yrs, range 6.1–13.1 yrs; 104 oligoarticular JIA, 61 polyarticular, 20 systemic, and 34 enthesitis-related arthritis onset) were retrospectively evaluated. A dual-energy x-ray absorptiometry (DEXA) scan at the lumbar spine was performed in all subjects. Of these, 89 consecutive patients were followed up randomly and longitudinally with a second and a third DEXA evaluation. The data obtained were compared with 80 age-matched and sex-matched healthy subjects.Results.At the first DEXA, patients with JIA showed a reduced spine BMAD standard deviation score (SDS) in comparison to controls (p < 0.001). These results were confirmed when the subjects were divided into JIA subtypes (p < 0.005) with the exception of enthesitis-related arthritis onset. Spine BMAD SDS significantly correlated with JIA onset type (p < 0.01), age at JIA onset (p < 0.005), and flares (p = 0.008). The longitudinal evaluation showed that spine BMAD SDS did not significantly improve at the followup in comparison to controls, in all subsets with JIA except for systemic onset (p < 0.05). Spine BMAD correlated with sex (p < 0.01), systemic corticosteroid exposure (p < 0.01), the number of intraarticular corticosteroid injections (p < 0.01), the interval from last steroid injection (p < 0.05), erythrocyte sedimentation rate (p < 0.005), and C-reactive protein levels (p < 0.005).Conclusion.Patients with JIA have a low bone mass and, after a first increase due to therapy, do not reach a healthy condition over time despite our current more effective drugs. These patients have a high risk of osteoporosis in early adulthood. To reduce the risk and improve the bone mass, close monitoring of bone mineral density, better control of disease activity, physical activity, and intake of calcium and vitamin D are recommended. In patients with osteoporosis, therapeutic approaches including bisphosphonates should be considered.

scholarly journals A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Louie C. Alexander ◽  
Grant McHorse ◽  
Janet L. Huebner ◽  
Anne-Christine Bay-Jensen ◽  
Morten A. Karsdal ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Joint Inflammation ◽  
Cartilage Degradation ◽  
Womac Pain ◽  
Type Iii Collagen ◽  
Type I ◽  
Radiographic Imaging ◽  
Type Iii

Abstract Objective To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. Methods Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). Results BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. Conclusions To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.

scholarly journals Children with oligoarticular Juvenile Idiopathic Arthritis have skewed synovial monocyte polarization pattern with functional impairment – a distinct inflammatory pattern for oligoarticular juvenile arthritis

2020 ◽  
Author(s):  
Tobias Schmidt ◽  
Elisabet Berthold ◽  
Sabine Arve-Butler ◽  
Birgitta Gullstrand ◽  
Anki Mossberg ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Mrna Expression ◽  
Mrna Level ◽  
Western World ◽  
Polarization Pattern ◽  
Oligoarticular Juvenile Idiopathic Arthritis ◽  
Monocytes And Macrophages ◽  
Anti Inflammatory

Abstract Background Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA). Methods Paired synovial fluid, blood samples (n=13) and synovial biopsies (n=3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro . Monocyte/macrophage distribution, polarization and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence and in situ hybridization. Results Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNγ)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p<0.001), CD86 (p<0.001) and CD206 (p<0.001), but not CD163, as compared to paired circulating monocytes. Additionally, polarization was extensively explored at the mRNA level and synovial fluid monocytes differentially expressed classical markers of M1(IFNγ)/M2(IL-4) polarization compared to circulating monocytes. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p<0.01). Synovial fluid induced M2 markers (CD16 and CD206), but not M1 (CD40) or CD86 in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies. Conclusion Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies.

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