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

Abstract

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.