title: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.A. Shukla, DM, Senior Resident, MD, General Medicine; P. Gaur, PhD Student, MSc Biotechnology; A. Aggarwal, Professor, DM, Clinical Immunology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.
authors.forename: Anuj
authors.initials: A
authors.lastname: Shukla
authors.affiliation: From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.A. Shukla, DM, Senior Resident, MD, General Medicine; P. Gaur, PhD Student, MSc Biotechnology; A. Aggarwal, Professor, DM, Clinical Immunology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Gaur
authors.affiliation: From the Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.A. Shukla, DM, Senior Resident, MD, General Medicine; P. Gaur, PhD Student, MSc Biotechnology; A. Aggarwal, Professor, DM, Clinical Immunology, Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences. aa.amita@gmail.com amita@sgpgi.ac.in.
authors.forename: Amita
authors.initials: A
authors.lastname: Aggarwal
mesh_terms: D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012720:Severity of Illness Index; D019063:Tenascin / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019063:Tenascin
keywords: ACUTE-PHASE RESPONSE; INFLAMMATION; INNATE IMMUNE SYSTEM; JUVENILE SPONDYLOARTHROPATHY