Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients with ankylosing spondylitis: a pilot study

Clin Rheumatol. 2017 Aug;36(8):1819-1826. doi: 10.1007/s10067-017-3624-7. Epub 2017 Apr 22.

Abstract

The studies aimed to assess a set of biomarkers for their correlations with disease activity/severity of patients with ankylosing spondylitis (AS). A total of 24 AS patients were treated with etanercept and prospectively followed for 12 weeks. Serum levels of TNF-α, IFN-γ, TGF-β, IL6, IL15, IL17, MMP3, and MICA were measured at baseline and after treatment. The change of these biomarkers was analyzed for correlations with MRI indices for joint inflammation, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, AS Disease Activity Score, serum CRP, and ESR. The Wilcoxon rank sum test was used to compare the biomarker levels between pre- and post-treatment and between pre-treatment and controls. Both step-wise procedures based on the Akaike information criterion (AIC) and least absolute shrinkage and selection operator with fivefold cross-validation were used to select the best model for pairwise correlations between the above clinical measures and the serum biomarkers. Serum levels of both MMP3 and IL6 were significantly higher in AS patients at baseline. After treatment, the levels of MMP3 decreased, but TGF-β and TNF-α increased significantly. The changes of serum MMP3 and MICA were significantly associated with MRI sacroiliac joint (SIJ) scores. CRP was positively correlated with serum MMP3 and IL6. The pattern of combined changes of serum MICA, MMP3, TGF-β, IL17, TNF-α, and IFN-γ predicted the MRI score of SIJ by logistic regression analysis. Specific serum biomarkers were significantly associated with clinical measures of AS. Most prominently, serum MMP3 level was found to have a positive correlation with the MRI score of SIJ and CRP. Serum MICA level negatively correlated with disease remission.

Keywords: Ankylosing spondylitis; Biomarkers; IL6; MICA; MMP3; MRI.

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cytokines / blood
  • Etanercept / therapeutic use*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Sacroiliac Joint / diagnostic imaging
  • Severity of Illness Index
  • Spondylitis, Ankylosing / blood*
  • Spondylitis, Ankylosing / diagnostic imaging
  • Spondylitis, Ankylosing / drug therapy*
  • Treatment Outcome
  • Young Adult

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Cytokines
  • C-Reactive Protein
  • Matrix Metalloproteinase 3
  • Etanercept