Background/Purpose Tenascin-C (TNC) is an extracellular matrix glycoprotein, which binds to TLR4 and leads to its activation. Monocytes of children with Enthesitis related arthritis (ERA) show TLR4 overexpression. TNC may serve as an endogenous stimulator of TLR4 in ERA. Thus we studied the serum and synovial fluid levels of TNC in children with ERA and its association with disease activity.

Methods TNC levels were measured in serum of 80 children with ERA satisfying ILAR criteria. 15 children were followed-up while on regular NSAID treatment and levels were reassessed at 3 months. 17 paired serum-synovial fluid samples and 25 healthy control serum samples were also analyzed. Disease activity was assessed by physician global assessment; tender, swollen and damaged joint counts; enthesitis score, ESR and CRP.

Results Patients were mainly boys (9:1) with average age at disease onset of 11.2 years and duration of disease of 4.4 years. 80% had peripheral arthritis, 63% active enthesitis, 43% clinical sacroilitis, 39% inflammatory back-pain, and 8% had a history of acute anterior uveitis. Most of the children were HLA-B27 positive (90%, n=72) and 29% had positive history of JIA-ERA or spondyloarthritis in the family.

The average physician global assessment (0-10) was 4.5±2.2. Average early morning stiffness was 50±57 minutes with 4±4-tender and 3±3-swollen joints. Average ESR and CRP were 72±37 mm at 1 hour and 6.9±5.6 mg/dl. 25% children had at least one damaged joint with an average count of 2±2. 16 children out of 80 had no tender and swollen joints and were classified as inactive disease.

The mean serum TNC level in children with active disease was 67.1±44.9 ng/ml and was significantly higher than the inactive 40.6±36.7 ng/ml (p=0.01) and healthy control 21±15.2 ng/ml (p<0.001). Median levels were higher in HLA-B27 positive 70.1 ng/ml vs. negative disease 22.8 ng/ml (p=0.003).

Serum levels correlated positively with disease activity parameters like physician global assessment (r=0.4, 95%CI=0.15 to 0.58, p=0.001), early morning stiffness (r=0.34, 95% CI = 0.1 to 0.55, p=0.005), tender joint count (r=0.4, 95%CI=0.2 to 0.6, p=0.0003), swollen joint count (r=0.46, 95%CI=0.27 to 0.6, p<0.0001), ESR (r=0.42, 95%CI=0.21 to 0.6, p=0.0002) and CRP (r=0.32, 95%CI=0.1 to 0.5, p=0.007) and negatively with duration of disease (r=-0.33, 95%CI=-0.5 to -0.17, p=0.003). TNC levels did not correlate with enthesitis scores and damaged joint counts. In ROC analysis for active vs. inactive disease, TNC (AUC=0.754) was equivalent to ESR (AUC=0.787) and CRP (AUC=0.789).

Treatment with regular and adequate dose of NSAIDs lead to a significant fall in the serum levels at 3 months of follow-up (p=0.0003). The median synovial fluid TNC level in JIA-ERA was 17.39 ng/ml.  Synovial fluid levels were significantly lower than the paired serum values (p=0.01).

Conclusion Circulating TNC levels are significantly raised and correlate with various clinical and laboratory parameters of disease activity in children with ERA. It is equivalent to ESR and CRP as a measure of disease activity. Regular NSAID treatment results in significant fall in the levels at 3 months probably related to control of disease activity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tenascin-c-a-tlr4-ligand-levels-in-enthesitis-related-arthritis-category-of-juvenile-idiopathic-arthritis-cross-sectional-and-longitudinal-study/