The Effects of TNF-α Inhibition on the Metabolism of Cartilage: Relationship between KS, HA, HAPLN1 and ADAMTS4, ADAMTS5, TOS and TGF-β1 Plasma Concentrations in Patients with Juvenile Idiopathic Arthritis.

Abstract

We assessed the effect of 24-month anti-tumor necrosis factor alpha (TNF-α) treatment on the remodeling of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: Quantitative evaluation of keratan sulfate (KS), hyaluronic acid (HA), hyaluronan and proteoglycan link protein 1 (HAPLN1), as potential biomarkers of joint dysfunction, and the levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5, total oxidative status (TOS) and transforming growth factor (TGF-β1) was performed (using immunoenzymatic methods) in blood obtained from patients before and after 24 months of etanercept (ETA) treatment. Results: When compared to the controls, KS, HA and HAPLN1 levels were significantly higher in patients with an aggressive course of JIA qualified for ETA treatment. An anti-cytokine therapy leading to clinical improvement promotes the normalization only of the HA level. Proteolytic and pro-oxidative factors, present in high concentrations in patients before the treatment, correlated with HAPLN1, but not with KS and HA levels. In these patients, negative correlations were found between the levels of TGF-β1 and KS, HA and HAPLN1. Conclusion: The anti-TNF-α therapy used in patients with JIA has a beneficial effect on ECM cartilage metabolism, but it does not completely regenerate it. The changes in the plasma HA level during the anti-cytokine therapy suggest its potential diagnostic utility in monitoring of disease activity and may be used to assess the efficacy of ETA treatment.