Reduction in TIMP-2 serum levels predicts remission of inflammatory bowel diseases

Eur J Clin Invest. 2018 Oct;48(10):e13002. doi: 10.1111/eci.13002. Epub 2018 Aug 6.

Abstract

Background: Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse.

Material & methods: In this prospective pilot study, a cohort of IBD patients (n = 32) was enrolled and treated with monoclonal anti-TNF-α antibodies. Patients were clinically followed up for a median period of 54 weeks. Serum circulating levels of C-reactive protein (CRP), TIMP-1 and -2, matrix metalloproteinase (MMP)-9 and -8, myeloperoxidase (MPO) and neutrophil elastase (NE) were assessed by ELISA at enrolment and at the end of the treatment.

Results: The percentage (%) TIMP-2 reduction from baseline to end of treatment was independently associated with IBD remission at the end of treatment and follow-up as well. ROC curve analysis further confirmed the good prognostic accuracy of % TIMP-2 reduction over the treatment period. Conversely, no other change in inflammatory molecule concentrations was able to predict short- or long-term IBD remission.

Conclusions: This study indicates TIMP-2 reduction during IBD treatment with monoclonal anti-TNF-α antibodies as a potential prognostic parameter of short and long term remission. To understand if TIMP-2 is an innocent biomarker or an active pathophysiological factor in IBD remains to be clarified.

Keywords: inflammation; inflammatory bowel diseases; matrix metalloproteinases; monoclonal antibodies; tissue inhibitor of matrix metalloproteinase-2.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Area Under Curve
  • Biomarkers / metabolism
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / drug therapy*
  • Male
  • Mesalamine / therapeutic use
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Remission Induction
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Immunosuppressive Agents
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2
  • Mesalamine