Connective Tissue Metabolism in Patients With Juvenile Idiopathic Arthritis: 10-Year Follow-Up Study

Panko, N; Shevchenko, N.S.; Rakovska, Liudmyla; Holovko, Tetiana

doi:10.35339/ic.6.1.5-11

Cited by 3 publications

(4 citation statements)

References 10 publications

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“…Significantly lower urinary concentrations of sGAGs in JIA patients, especially in the afflicted girls, compared with healthy children, did not normalize with disease-modifying treatment with MTX, SSA, and EC, as well as with anti-cytokine treatment. The results obtained are consistent with the results of the research of other authors [4,19]. It should be pointed out, however, that Shevchenko et al [19] evaluated glycan levels by measuring daily urinary excretion of uronic acids in patients with different durations of JIA.…”

Section: Discussionsupporting

confidence: 89%

“…The results obtained are consistent with the results of the research of other authors [4,19]. It should be pointed out, however, that Shevchenko et al [19] evaluated glycan levels by measuring daily urinary excretion of uronic acids in patients with different durations of JIA. The researchers observed lower urinary concentrations of the tested markers, especially in patients with a disease duration of 13 to 24 months.…”

Section: Discussionsupporting

confidence: 89%

“…Moreover, contrary to our results, in the female patients, the authors showed higher concentrations of uronic acids compared to the results obtained in the male group and the whole group of healthy subjects, without taking their gender into account. Females, according to the cited researchers, are predisposed to the development of osteoarthritis secondary to JIA [19].…”

Section: Discussionmentioning

confidence: 99%

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Investigation of Glycosaminoglycans in Urine and Their Alteration in Patients with Juvenile Idiopathic Arthritis

Lato-Kariakin,

Kuźnik-Trocha,

Gruenpeter

et al. 2023

Biomolecules

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(1) Background: In this study, we evaluated the modulation of urine glycosaminoglycans (GAGs), which resulted from etanercept (ETA) therapy in patients with juvenile idiopathic arthritis (JIA) in whom methotrexate therapy failed to improve their clinical condition. (2) Methods: The sulfated GAGs (sGAGs, by complexation with blue 1,9-dimethylmethylene), including chondroitin–dermatan sulfate (CS/DS) and heparan sulfate (HS), as well as non-sulfated hyaluronic acid (HA, using the immunoenzymatic method), were determined in the blood of 89 children, i.e., 30 healthy children and 59 patients with JIA both before and during two years of ETA treatment. (3) Results: We confirmed the remodeling of the urinary glycan profile of JIA patients. The decrease in the excretion of sGAGs (p < 0.05), resulting from a decrease in the concentration of the dominant fraction in the urine, i.e., CS/DS (p < 0.05), not compensated by an increase in the concentration of HS (p < 0.000005) and HA (p < 0.0005) in the urine of patients with the active disease, was found. The applied biological therapy, leading to clinical improvement in patients, at the same time, did not contribute to normalization of the concentration of sGAGs (p < 0.01) in the urine of patients, as well as CS/DS (p < 0.05) in the urine of sick girls, while it promoted equalization of HS and HA concentrations. These results indicate an inhibition of the destruction of connective tissue structures but do not indicate their complete regeneration. (4) Conclusions: The metabolisms of glycans during JIA, reflected in their urine profile, depend on the patient’s sex and the severity of the inflammatory process. The remodeling pattern of urinary glycans observed in patients with JIA indicates the different roles of individual types of GAGs in the pathogenesis of osteoarticular disorders in sick children. Furthermore, the lack of normalization of urinary GAG levels in treated patients suggests the need for continued therapy and continuous monitoring of its effectiveness, which will contribute to the complete regeneration of the ECM components of the connective tissue and thus protect the patient against possible disability.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Investigation of Glycosaminoglycans in Urine and Their Alteration in Patients with Juvenile Idiopathic Arthritis

Lato-Kariakin,

Kuźnik-Trocha,

Gruenpeter

et al. 2023

Biomolecules

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“…In contrast, plasma levels of dermatan sulfates, hyaluronic acid, and keratan sulfates increased, while heparan sulfates did not change in these patients. Based on these studies, it can be concluded that different types of GAGs respond differently to factors leading to the manifestation of pathological changes of the osteoarticular system in children with JIA [ 5 , 23 , 24 , 25 , 26 ]. For instance, excessive release of DS chains and HA chains of lower molecular mass seem to contribute to JIA onset.…”

Section: Discussionmentioning

confidence: 99%

GAAGs, COMP, and YKL-40 as Potential Markers of Cartilage Turnover in Blood of Children with Juvenile Idiopathic Arthritis Treated with Etanercept—Relationship with ADAMTS4, ADAMTS5, and PDGF-BB

Dąbkowska

Wojdas

Kuźnik-Trocha

et al. 2022

JCM

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We quantified galactosaminoglycans (GAAGs), oligomeric cartilage matrix protein (COMP), and human cartilage glycoprotein 39 (YKL-40) in blood obtained from juvenile idiopathic arthritis (JIA) before and during 2-year treatment with etanercept (ETA), as potential biomarkers of cartilage extracellular matrix (ECM) dysfunction and indicators of efficacy of biologic therapy. We also evaluated the relationship of the mentioned markers with the factors that regulate their metabolism, disintegrin and thrombospondin motif metalloproteinases 4 (ADAMTS4), ADAMTS5, and platelet-derived growth factor BB (PDGF-BB). Methods: We studied 38 children diagnosed with JIA and 45 healthy children. We quantified GAAGs by assessing the concentration of unsaturated disaccharide units formed by digestion of isolated glycosaminoglycans with chondroitinase ABC, while COMP, YKL-40, and PDGF-BB were quantified using immunoenzymatic methods. Results: Compared to the control group, GAAGs and COMP levels were significantly lower, while YKL-40 levels were higher in the blood of patients with aggressive JIA, qualified for ETA treatment. ETA therapy leading to clinical improvement simultaneously promoted normalization of COMP and YKL-40 levels, but not GAAGs. After 24 months of taking ETA, glycan levels were still significantly lower, relative to controls. GAAGs, COMP, and YKL-40 levels were significantly influenced by ADAMTS4, ADAMTS5, and PDGF-BB levels both before and during ETA treatment. Conclusions: The dynamics of changes in marker concentrations during treatment seem to indicate that measurement of COMP and YKL-40 levels can be used to assess the chondroprotective biological efficacy of therapy. In contrast, changes in GAAGs concentrations reflect systemic extracellular matrix transformations in the course of JIA.

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Plasma Glycosaminoglycans in Children with Juvenile Idiopathic Arthritis Being Treated with Etanercept as Potential Biomarkers of Joint Dysfunction

et al. 2022

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We assessed the effect of two-year etanercept (ETA) therapy on the metabolism of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: We performed a quantitative evaluation of glycosaminoglycans (GAGs) (performed by the multistage extraction and purification method) in blood obtained from patients before and during 24 months of ETA treatment, as potential biomarker of joint dysfunction and indicators of biological effectiveness of therapy. Since the metabolism of GAGs is related to the activity of proteolytic enzymes and prooxidant–antioxidant factors, we decided to evaluate the relationship between GAGs and the levels of metalloproteinases (MMP), i.e., MMP-1 and MMP-3 (using immunoenzymatic methods), as well as the total antioxidative status (TAS) (using the colorimetric method) in blood of the JIA patients. Results: When compared to the controls, GAGs and TAS concentrations were significantly lower in patients with an aggressive course of JIA qualified for ETA treatment. MMP-1 and MMP-3 levels were significantly higher versus control values. An anti-cytokine therapy leading to clinical improvement does not lead to the normalization of any of the assessed parameters. GAGs concentration is significantly related to MMP-1, MMP-3, TAS, TOS, and CRP levels. Conclusion: The results of the present study indicate the necessity of constant monitoring of the dynamics of destructive processes of articular cartilage in children with JIA. We suggest that GAGs may be a useful biomarker to assess the clinical status of the extracellular matrix of joints.

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Connective Tissue Metabolism in Patients With Juvenile Idiopathic Arthritis: 10-Year Follow-Up Study

Cited by 3 publications

References 10 publications

Investigation of Glycosaminoglycans in Urine and Their Alteration in Patients with Juvenile Idiopathic Arthritis

Investigation of Glycosaminoglycans in Urine and Their Alteration in Patients with Juvenile Idiopathic Arthritis

GAAGs, COMP, and YKL-40 as Potential Markers of Cartilage Turnover in Blood of Children with Juvenile Idiopathic Arthritis Treated with Etanercept—Relationship with ADAMTS4, ADAMTS5, and PDGF-BB

Plasma Glycosaminoglycans in Children with Juvenile Idiopathic Arthritis Being Treated with Etanercept as Potential Biomarkers of Joint Dysfunction

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