Concerted Actions by PIICP, CTXII, and TNF-α in Patients with Juvenile Idiopathic Arthritis

Abstract

Joint destruction in juvenile idiopathic arthritis (JIA), initiated in the early, preclinical stage of the disease, is diagnosed on the basis of clinical evaluation and radiographic imaging. The determination of circulating cartilage-matrix turnover markers can facilitate the diagnosis and application of better and earlier treatment strategies for JIA. We have shown that 96 JIA patients have elevated levels of procollagen II C-terminal propeptide (PIICP), reflecting the extent of joint cartilage biosynthesis, and C-telopeptide of type II collagen (CTXII), a biomarker of the resorption of this tissue. Patients who did not respond to treatment had particularly high levels of these markers. JIA treatment resulted in the normalization of these markers in remissive patients, but not in those with active JIA. We showed correlations between examined variables and inflammatory process indicators, i.e., C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and tumor necrosis factor-α (TNF-α). The TNF-α of patients responding to treatment correlated with PIICP, especially in the patients before treatment (r = 0.898, p < 0.001). Significant changes in serum PIICP during JIA therapy suggest its potential diagnostic utility in the monitoring of disease activity and the possibility of its use in assessing treatment towards remission. Understanding changes in type II collagen metabolism over the course of the discussed arthritis may allow the implementation of both new diagnostic tools and new therapeutic strategies in children with JIA.

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

“…Applying the appropriate treatment too late, due to the lack of specific diagnostic biomarkers, may result in the perpetuation of pathological changes in the motor system in patients, especially in those with high disease activity who require a biological therapy. As we proved in our previous research, the biomarkers of the changes in the cartilage matrix can be both the components of the ECM and their derivatives, which are released into biological fluids in the course of metabolic transformations of these compounds [ 12 , 16 , 17 , 18 , 19 ]. We conducted studies involving children treated with methotrexate, which inhibits the development of arthropathy through a number of mechanisms, e.g., folate antagonism, adenosine signaling, generation of reactive oxygen species, decrease in adhesion molecules, alteration of cytokine and proteinases profiles or polyamine inhibition [ 20 ].…”

GAAGs, COMP, and YKL-40 as Potential Markers of Cartilage Turnover in Blood of Children with Juvenile Idiopathic Arthritis Treated with Etanercept—Relationship with ADAMTS4, ADAMTS5, and PDGF-BB

“…The biomarkers of cartilage transformations may be matrix components as well as their derivatives, which are released during metabolic transformations into biological fluids. In our previous studies, we evaluated specific markers of cartilage ECM remodeling, including procollagen II C-terminal propeptide (PIICP), C-telopeptide of type II collagen (CTXII) [ 10 ], hyaluronic acid, keratan sulfates, hyaluronan and proteoglycan link protein 1 [ 11 ], or metalloproteinases [ 12 ]. Considering the above, this study was designed to evaluate the yet unknown dynamics of changes in the levels of GAAGs, COMP, and YKL-40-as potential biomarkers of dysfunctions of the osteoarticular system and the efficacy of biological therapy in the blood of JIA patients before and during 2 years of treatment with TNF-α inhibitors.…”