title: Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis.
abstract: OBJECTIVE
  In prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in ankylosing spondylitis (AS). Several biomarkers have been identified as independent predictors of radiographic progression in rheumatoid arthritis, however, and these may be of use in AS. This study was undertaken to analyze serologic biomarkers as predictors of radiographic progression in AS.
  
  
  METHODS
  We measured a panel of biomarkers reflecting cartilage turnover and osteoclasis. These biomarkers were cartilage oligomeric matrix protein, human cartilage gp-39 (YKL-40), type II collagen epitopes detected by the C2C and C1,2C degradation assays and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix metalloproteinase 3 (MMP-3). The analysis was performed in a cohort of AS patients from the Netherlands, Belgium, and France enrolled in a longitudinal study, the Outcome Assessments in Ankylosing Spondylitis International Study. We examined 2-year radiographic progression data scored using the modified Stoke AS Spine Score (mSASSS).
  
  
  RESULTS
  Complete data were available on 97 patients. Only the biomarkers YKL-40 and MMP-3 showed weak to moderate univariate correlation with 2-year progression. After adjustment for sex, age, disease duration, C-reactive protein level, and baseline mSASSS, only MMP-3 was significantly associated with 2-year progression (beta = 0.29, P = 0.004). Logistic regression analysis revealed MMP-3 (cutoff 68 ng/ml; odds ratio 9.4 [95% confidence interval 1.6-56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 18.6 [95% confidence interval 2.5-138]) as the only independent predictors of 2-year progression (cutoff 3 mSASSS units; model R(2) = 50%). MMP-3 was primarily contributory in patients who already had substantial baseline damage (>10 mSASSS units).
  
  
  CONCLUSIONS
  These results indicate that MMP-3 is a significant independent predictor of radiographic progression in patients with AS, particularly in those with preexisting radiographic damage.
authors.affiliation: University of Alberta, Edmonton, Alberta, Canada. walter.maksymowych@ualberta.ca
authors.forename: Walter P
authors.initials: WP
authors.lastname: Maksymowych
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.forename: Barbara
authors.initials: B
authors.lastname: Conner-Spady
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Herman
authors.initials: H
authors.lastname: Mielants
authors.forename: Hille
authors.initials: H
authors.lastname: van der Tempel
authors.forename: A Robin
authors.initials: AR
authors.lastname: Poole
authors.forename: Nandi
authors.initials: N
authors.lastname: Wang
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002356:Cartilage / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011859:Radiography; D012720:Severity of Illness Index; D013131:Spine / Q000000981:diagnostic imaging / Q000473:pathology*; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D019278:Matrix Metalloproteinase 3