Neutrophil Gelatinase B-associated Lipocalin and Matrix metalloproteinase-9 Complex as a Surrogate Serum Marker of Mucosal Healing in Ulcerative Colitis

Inflamm Bowel Dis. 2014 Jul;20(7):1198-207. doi: 10.1097/MIB.0000000000000068.

Abstract

Background: The current standard for the assessment of mucosal healing after therapy in inflammatory bowel diseases is endoscopy. However, a high need exists for noninvasive, accurate surrogate markers.

Methods: In 2 independent cohorts, levels of serum neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 complex (NGAL-MMP-9) from patients with active ulcerative colitis (UC) before and after first treatment with infliximab and from healthy controls (HC) were determined with zymography and sandwich enzyme-linked immunosorbent assay. The response to infliximab was defined as complete mucosal healing (Mayo endoscopic subscore 0-1) at control endoscopy. Data were analyzed with SPSS, and P values <0.05 were considered significant.

Results: In cohort 1 (n = 66; median age, 30 yr; 38% female), serum NGAL-MMP-9 levels significantly increased at baseline in UC patients versus HC (103.8 versus 42.4 ng/mL; P < 0.0001), whereas 55% of the patients had normal C-reactive protein levels. NGAL-MMP-9 levels significantly decreased after therapy in UC responders (from 116.3 ng/mL to 32.0 ng/mL; P < 0.0001) and in nonresponders (from 94.7 ng/mL to 54.1 ng/mL; P = 0.047). In cohort 2 (n = 132; median age, 39 yr; 53% female), NGAL-MMP-9 levels increased at baseline in active UC patients versus HC (86.5 versus 60.4 ng/mL; P = 0.10), whereas 45% of the patients had normal C-reactive protein levels. NGAL-MMP-9 levels significantly decreased after therapy in responders (from 87.5 ng/mL to 16.3 ng/mL; P < 0.0001) but not in nonresponders (from 82.7 ng/mL to 57.8 ng/mL; P = 0.19). After pooling the data, a cutoff value of 97.7 ng/mL for NGAL-MMP-9 complex was determined to predict complete mucosal healing with high specificity (91%).

Conclusions: Serum NGAL-MMP-9 is suggested as a new surrogate marker for the assessment of mucosal healing in UC patients treated with infliximab.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Biomarkers / blood
  • Case-Control Studies
  • Colitis, Ulcerative / blood*
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / drug therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Infliximab
  • Intestinal Mucosa / drug effects
  • Lipocalins / blood*
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies
  • Severity of Illness Index
  • Treatment Outcome
  • Wound Healing / physiology*
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Lipocalins
  • Infliximab
  • Matrix Metalloproteinase 9