Tenascin-c levels, a toll-like receptor 4 ligand, in enthesitis-related arthritis category of juvenile idiopathic arthritis: A cross-sectional and longitudinal study

Abstract

Objective. Monocytes of children with enthesitis-related arthritis (ERA) show Toll-like receptor 4 (TLR4) overexpression. Tenascin-C (TNC) is an extracellular matrix glycoprotein and acts as an endogenous TLR4 ligand. Thus, we studied the serum and synovial fluid (SF) levels of TNC in children with ERA. Methods. TNC was measured in the serum of 80 children with ERA satisfying the International League of Associations for Rheumatology criteria. Fifteen children were followed up while being treated with regular nonsteroidal antiinflammatory drug (NSAID) therapy and levels were reassessed at 3 months. Seventeen paired serum-SF samples and 25 healthy control serum samples were also analyzed. Disease activity was assessed by physician's global assessment (PGA), early morning stiffness (EMS), tender (TJC) and swollen joint counts (SJC), enthesitis score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results. The mean serum TNC level in patients with active disease (67.1 ± 44.9 ng/ml) was significantly higher than in those with inactive disease (40.6 ± 36.7 ng/ml, p = 0.01) and healthy controls (21 ± 15.2 ng/ml, p < 0.001). Levels of TNC were higher in HLA-B27-positive (58.4 ng/ml) versus -negative disease (20.4 ng/ml, p = 0.01). TNC levels correlated moderately with disease activity: PGA r = 0.4, EMS r = 0.34, TJC r = 0.4, SJC r = 0.46, ESR r = 0.42, and CRP r = 0.32. In receiver-operation characteristic analysis for active versus inactive diseases, TNC [area under the curve (AUC) = 0.754] was equivalent to ESR (AUC = 0.787) and CRP (AUC = 0.789). Regular NSAID therapy led to a significant fall in serum TNC levels at 3 months (p = 0.0003). The SF TNC level was 17.39 ng/ml, significantly lower than the paired serum values (p = 0.01). Conclusion. Serum TNC levels are significantly raised and correlate with various clinical and laboratory variables of disease activity in children with ERA. Regular NSAID therapy reduces the TNC levels, probably related to controlling disease activity.