4.7 Article

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

Journal

JOURNAL OF CLINICAL MEDICINE
Volume 11, Issue 17, Pages -

Publisher

MDPI
DOI: 10.3390/jcm11175069

Keywords

juvenile idiopathic arthritis; etanercept; extracellular matrix turnover markers; galactosaminoglycans; oligomeric cartilage matrix protein; human cartilage glycoprotein 39

Funding

  1. Medical University of Silesia in Katowice, Poland [PCN-2-063/N/1/I]

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The levels of galactosaminoglycans (GAAGs) and oligomeric cartilage matrix protein (COMP) are significantly decreased, while the levels of human cartilage glycoprotein 39 (YKL-40) are increased in juvenile idiopathic arthritis (JIA) patients, which can serve as potential biomarkers for assessing the efficacy of biologic therapy. Treatment with etanercept (ETA) can normalize the levels of COMP and YKL-40, but does not significantly affect the levels of GAAGs. ADAMTS4, ADAMTS5, and PDGF-BB have significant influences on the levels of these markers.
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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