Wojdas Magdalena, Dąbkowska Klaudia, Kuźnik-Trocha Kornelia, Wisowski Grzegorz, Lachór-Motyka Iwona, Komosińska-Vassev Katarzyna, Olczyk Krystyna, Winsz-Szczotka Katarzyna
Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, ul. Jedności 8, 41-200 Sosnowiec, Poland.
Department of Rheumatology, The John Paul II Pediatric Center in Sosnowiec, ul. G. Zapolskiej 3, 41-218 Sosnowiec, Poland.
Biomedicines. 2022 Jul 31;10(8):1845. doi: 10.3390/biomedicines10081845.
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).
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.
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.
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.
我们评估了两年期依那西普(ETA)治疗对幼年特发性关节炎(JIA)患者软骨细胞外基质(ECM)代谢的影响。
我们对ETA治疗24个月之前及治疗期间从患者采集的血液中的糖胺聚糖(GAGs)(采用多阶段提取和纯化方法进行检测)进行了定量评估,将其作为关节功能障碍的潜在生物标志物以及治疗生物学有效性的指标。由于GAGs的代谢与蛋白水解酶和促氧化剂 - 抗氧化剂因子的活性相关,我们决定评估JIA患者血液中GAGs与金属蛋白酶(MMP)水平之间的关系,即MMP - 1和MMP - 3(采用免疫酶法),以及总抗氧化状态(TAS)(采用比色法)。
与对照组相比,符合ETA治疗条件的侵袭性JIA患者的GAGs和TAS浓度显著降低。MMP - 1和MMP - 3水平显著高于对照值。导致临床改善的抗细胞因子治疗并未使任何评估参数恢复正常。GAGs浓度与MMP - 1、MMP - 3、TAS、TOS和CRP水平显著相关。
本研究结果表明有必要持续监测JIA患儿关节软骨破坏过程的动态变化。我们认为GAGs可能是评估关节细胞外基质临床状态的有用生物标志物。