title: Serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis: effect of TNFalpha antagonist therapy.
abstract: OBJECTIVE
  To measure serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis (AS) and in controls and to look for changes in these variables during TNFalpha antagonist therapy.
  
  
  METHODS
  We prospectively studied a group of patients who met New York criteria for AS and a group of healthy volunteers. We recorded age, disease duration, main features of the disease, BASDAI, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Serum MMP-3 and cathepsin K were assayed in duplicate using ELISA kits (Quantikine MMP-3, R&D Systems; and Cathepsin K, Biomedica). We also assayed IL-17 (Quantikine IL-17, R&D Systems) and BMP-7 (human BMP-7 DuoSet, R&D Systems). In patients treated with TNFalpha antagonists, the assays were repeated 10 weeks after treatment initiation. The Mann-Whitney test was used for between-group comparisons and the Wilcoxon test for evaluations of changes under treatment. Correlation testing was performed. P-values less than 0.05 were considered significant.
  
  
  RESULTS
  We studied 23 outpatients with AS and 21 controls, with mean age of 39.9 years and 41.2 years, respectively (NS). Disease duration was 10.1 years (1.3); most patients had axial disease (n=21) and carried HLA-B27 (n=19). At baseline, the mean BASDAI was 44.1 mm (4.1) and the mean CRP level was 22.3 mg/L (4.7). Serum MMP-3 levels were significantly higher in the patients than in the controls (4.71 vs. 2.79 ng/ml, P=0.04); levels were also higher for cathepsin K (6.4 vs. 3.6 pg/ml) and IL-17 (60.4 vs. 32 pg/ml), but the differences were not statistically significant. No difference was noted for BMP-7. The only positive correlation was between the ESR and the CRP level (P=0.0002). Thirteen patients were evaluated 10 weeks into TNFalpha antagonist therapy (adalimumab, n=7; etanercept, n=4; or infliximab, n=2). Serum MMP-3 decreased significantly (P=0.04); significant decreases were also noted for the ESR, CRP, and BASDAI.
  
  
  CONCLUSIONS
  MMP-3 is significantly increased in patients with active AS but fails to correlate significantly with conventional variables used to assess disease activity. TNFalpha antagonist therapy induces a significant decrease in MMP-3 levels, together with decreases in conventional variables (ESR, CRP, and BASDAI). MMP-3 may be a biomarker for disease activity in AS but supplies no additional information to the clinician.
authors.affiliation: Service de Rhumatologie, CHU Jean Minjoz et, EA 3186, Université de Franche-Comté, Boulevard Fleming, 25030 Besançon, France. dwendling@chu-besancon.fr
authors.forename: Daniel
authors.initials: D
authors.lastname: Wendling
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cedoz
authors.forename: Evelyne
authors.initials: E
authors.lastname: Racadot
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D056657:Cathepsin K; D002403:Cathepsins / Q000097:blood*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D066298:In Vitro Techniques; D000069285:Infliximab; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D019278:Matrix Metalloproteinase 3; D000068879:Adalimumab; D000068800:Etanercept