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

de Bruyn, Magali MSc*,†; Arijs, Ingrid PhD; Wollants, Willem-Jan Dipl Ing; Machiels, Kathleen MSc; Van Steen, Kristel PhD; Van Assche, Gert MD, PhD; Ferrante, Marc MD, PhD; Rutgeerts, Paul MD, PhD; Vermeire, Séverine MD, PhD; Opdenakker, Ghislain MD, PhD*

doi: 10.1097/MIB.0000000000000068
Original Clinical Articles

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.

Article first published online 27 May 2014.Supplemental Digital Content is Available in the Text.

*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.

Reprints: Ghislain Opdenakker, MD, PhD, Department of Microbiology and Immunology, Rega Institute for Medical Research, Minderbroedersstraat 10, blok x-bus 1030, Leuven 3000, Belgium (e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

I. Arijs and M. Ferrante are postdoctoral fellows and S. Vermeire is a Senior Clinical Investigator of the Fund for Scientific Research of Flanders (FWO-Vlaanderen). M. de Bruyn is a PhD student funded by a fellowship from the Agency for Innovation by Science and Technology (IWT). P. Rutgeerts, S. Vermeire, G. Van Assche and M. Ferrante report following conflicts of interest: grant support, lecture fees and consulting fees from Centocor and Schering-Plough. Supported by FWO-Vlaanderen and “Geconcerteerde Onderzoeksacties GOA 2013-014”.

Received November 05, 2013

Accepted April 03, 2014

© Crohn's & Colitis Foundation of America, Inc.
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