Juvenile idiopathic arthritis patients have a distinct cartilage and bone biomarker profile that differs from healthy and knee-injured children

Abstract

ObjectiveJoint destruction is a hallmark of juvenile idiopathic arthritis (JIA). Clinical evaluation and radiographic imaging are current methods to identify destruction. Biomarkers could aid an earlier and more sensitive diagnosis. Our aim was to investigate levels of bone and cartilage degradation biomarkers in JIA patients, compared to healthy children or juveniles with knee injuries. Methods Triple-paired synovial fluid, plasma and urine samples from 29 JIA patients were compared to 61 plasma samples from healthy children and synovial fluid from 41 knee-injured juveniles. Cartilage biomarkers ARGS neoepitope of aggrecan (ARGS), cartilage oligomeric matrix protein (COMP), type II collagen epitope (C2C), bone biomarkers N-terminal type Icollagen cross-linked telopeptide (NTX-I) and tartrate-resistant acid phosphatase 5b (TRAP5b) were analysed by immunoassays. Results Plasma levels of ARGS, C2C, COMP and TRAP5bwere increased in JIA compared to healthy children. Compared to knee-injured juveniles, synovial fluid C2C and TRAP5b were increased in JIA, while ARGS and COMP were decreased. For JIA patients, local (synovial fluid) and systemic (plasma/urine) levels of bone biomarkers correlated positively; age correlated negatively to plasma levels of C2C and TRAP5b; no correlation was found between biomarkers and gender, affected joint count, disease duration or medication. Conclusion Elevated levels of destruction biomarkers in JIA compared to healthy children indicate a potential to serve as clinicaltools for destructive joint disease. High levels of TRAP5b, NTX-I and collagen II in JIA in contrast to more pronounced aggrecan and COMP degradation in juvenile knee injuries, suggests that JIA patients have a unique biomarker pattern, different from healthy and knee-injured children.

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

“…Thus, our results and those of Bjørnhart et al [ 43 ] and Urakami et al [ 44 ] confirm the above thesis. In contrast to our results, Struglics et al [ 40 ] showed that JIA patients are characterized by an increase in blood COMP levels. These discrepancies are likely the result of the cited authors’ qualification of patients into three types of arthropathy, different disease duration, and inconsistent pharmacotherapy, which might determine the turnover of the ECM, since we have shown that COMP metabolism in patients with JIA, both before and during ETA therapy, remains related to the activity of proteolytic processes, stimulated by ADAMTS4 and ADAMTS5 concentrations, as well as anabolic processes, related to PDGF-BB concentrations.…”

“…This confirms the significant structural abnormalities of the cartilage matrix in children with JIA. This is due to the fact that predominant tissue localization of COMP is articular cartilage, while small amounts of the protein in question are also found in tendons, meniscus, or synovial membrane [ 40 ]. Deficiency of this protein may, on the one hand, promote the degradation of collagenous cartilage tissue, but on the other hand, COMP deficiency may result from pathological joint remodeling of the ECM.…”