Serum CS/DS, IGF-1, and IGFBP-3 as Biomarkers of Cartilage Remodeling in Juvenile Idiopathic Arthritis: Diagnostic and Therapeutic Implications.

Cartilage destruction in juvenile idiopathic arthritis (JIA) is diagnosed, often too late, on basis of clinical evaluation and radiographic imaging. This case-control study investigated serum chondroitin/dermatan sulfate (CS/DS) as a potential biochemical marker of cartilage metabolism, aiming to improve early diagnosis and precision treatment for JIA. We also measured the levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) (using ELISA methods) in JIA patients (n = 55) both before and after treatment (prednisone, sulfasalazine, methotrexate, administered together), and analyzed their relationships with CS/DS levels. Untreated JIA patients [8.26 µg/mL (6.25-9.66)], especially untreated girls [8.57 µg/mL (8.13-9.78)] and patients with a polyarticular form of the disease [7.09 µg/mL (5.63-8.41)], had significantly reduced levels of serum CS/DS compared with the control [14.48 µg/mL (10.23-15.77)]. Therapy resulted in a significant increase in this parameter, but without normalization. We also found significantly lower levels of IGF-1 [66.04 ng/mL (49.45-96.80)] and IGFBP-3 [3.37 ng/mL (2.65-4.88)] in untreated patients compared with the control [96.92 ng/mL (76.04-128.59), 4.84 ng/mL (4.21-7.750), respectively]. Based on receiver operating characteristic (ROC) curve analysis, the blood concentration of CS/DS demonstrated the highest diagnostic power (AUC = 0.947) for JIA among all the tested markers. Untreated patients showed significant correlations between CS/DS and IGF-1 (r = -0.579, p = 0.0000), IGFBP-3 (r = -0.506, p = 0.0001), and C-reactive protein (r = 0.601, p = 0.0005). The observed changes in CS/DS during the course of JIA, influenced by both impairment of the IGF/IGFBP axis and inflammation, indicate the need for continued therapy to protect patients from potential disability. We suggest that CS/DS may be a useful biomarker of disease activity and could be employed to assess treatment efficacy and progress toward remission.