Influence of proteolytic-antiproteolytic enzymes and prooxidative-antioxidative factors on proteoglycan alterations in children with juvenile idiopathic arthritis.

Clinical biochemistry

PubMedID: 24495859

Winsz-Szczotka K, Komosinska-Vassev K, Kuznik-Trocha K, Gruenpeter A, Lachór-Motyka I, Olczyk K. Influence of proteolytic-antiproteolytic enzymes and prooxidative-antioxidative factors on proteoglycan alterations in children with juvenile idiopathic arthritis. Clin Biochem. 2014;.
OBJECTIVES
The influence of proteolytic-antiproteolytic enzymes and prooxidative-anti-oxidative factors on proteoglycan alterations in children with juvenile idiopathic arthritis (JIA), were evaluated in this study.

DESIGN, METHODS, RESULTS
Plasma and urinary glycosaminoglycans (GAGs), as well as plasma levels of matrix metalloproteinases (MMPs)-3, MMP-10, tissue inhibitors of metalloproteinases (TIMPs)-1, TIMP-2, total oxidative status (TOS) and total antioxidative status (TAS) were quantified in samples obtained from 30 healthy subjects and 30 JIA patients before and after treatment. Significantly decreased plasma and urinary concentration of GAGs in JIA patients before treatment was observed. Therapy resulted in an increase in the concentration of the above listed parameters. However, the plasma GAGs level still remained significantly lower compared to controls. Increased levels of MMP-3 and TIMP-1 in both JIA patient groups were recorded. The plasma MMP-10 and TIMP-2 concentrations in untreated patients were significantly decreased. Anti-inflammatory treatment led to normalisation of these parameters concentrations. Significant increase of TOS but decrease of TAS, were found in the blood of untreated patients. The treatment resulted only in the normalisation of TOS concentration. We have revealed a significant correlation between plasma GAGs and: MMP-3 (r=0.54), TOS (r=0.64) and urinary GAGs (r=0.55), respectively.

CONCLUSIONS
Proteoglycans/glycosaminoglycans alteration in JIA patients, which are stimulated by MMP-3 and reactive oxygen species (ROS), indicate rather systemic disturbance of extracellular matrix metabolism, and not merely local changes which occur in articular structures. Given the destructive potential of ROS and MMPs and their hyperexpression in JIA, inhibition of these compounds should bring a substantial clinical benefit.