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.
*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: email@example.com).
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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