title: Neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 complex as a surrogate serum marker of mucosal healing in ulcerative colitis.
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.
authors.affiliation: *Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium; †Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium; and ‡Montefiore Institute, Electrical Engineering and Computer Science, University of Liège, Liège, Belgium.
authors.forename: Magali
authors.initials: M
authors.lastname: de Bruyn
authors.forename: Ingrid
authors.initials: I
authors.lastname: Arijs
authors.forename: Willem-Jan
authors.initials: WJ
authors.lastname: Wollants
authors.forename: Kathleen
authors.initials: K
authors.lastname: Machiels
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Steen
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000187:drug effects; D054834:Lipocalins / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014945:Wound Healing / Q000502:physiology*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D054834:Lipocalins; D000069285:Infliximab; D020780:Matrix Metalloproteinase 9