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Fecal MMP-9: A New Noninvasive Differential Diagnostic and Activity Marker in Ulcerative Colitis

Annaházi, Anita MD*,†; Molnár, Tamás MD, PhD*; Farkas, Klaudia MD, PhD*; Rosztóczy, András MD, PhD*; Izbéki, Ferenc MD, PhD*; Gecse, Krisztina MD, PhD*; Inczefi, Orsolya MD*; Nagy, Ferenc MD, PhD*; Földesi, Imre PhD*; Szűcs, Mónika MSc; Dabek, Marta PhD; Ferrier, Laurent PhD; Theodorou, Vassilia PhD; Bueno, Lionel PhD; Wittmann, Tibor MD, PhD*; Róka, Richárd MD, PhD*

doi: 10.1002/ibd.22996
Original Clinical Articles

Background: Ulcerative colitis (UC) is characterized by frequent relapses, with the presence of colorectal inflammation and mucosal lesions. Matrix-metalloprotease 9 (MMP-9) is elevated in colonic biopsies, urine, and blood plasma of UC patients. MMP-9 has been suggested as a predictor of UC in the urine of children; however, 20% of the controls tested positive. So far, fecal MMP-9 levels have never been measured. Our aims were: 1) to compare fecal MMP-9 levels in UC patients to control subjects and a functional gastrointestinal disorder characterized by diarrhea (IBS-D); 2) to test the correlation between UC disease activity and fecal levels of MMP-9; and 3) to correlate fecal MMP-9 levels with a known fecal marker of UC activity, calprotectin.

Methods: UC (n = 47), IBS-D (n = 23) patients, and control subjects (n = 24) provided fecal samples for MMP-9 analysis. In UC patients, disease severity was evaluated by the Mayo score. Fecal MMP-9 and calprotectin levels were measured by enzyme-linked immunosorbent assay and lateral flow assay, respectively.

Results: MMP-9 was undetectable or ≤0.22 ng/mL in the feces of all controls and IBS-D patients. In UC patients, fecal MMP-9 levels significantly correlated with the overall Mayo score (P < 0.001), the endoscopic score (P < 0.001), and the serum C-reactive protein levels (P = 0.002). Additionally, in UC patients fecal MMP-9 levels showed a significant correlation with a known disease activity marker, fecal calprotectin (P = 0.014).

Conclusions: These results highlight fecal MMP-9 as a useful tool in the differential diagnosis of diarrheic disorders and in the noninvasive evaluation of disease activity and mucosal healing in UC.

Article first published online 1 May 2012

*First Department of Medicine, University of Szeged, Szeged, Hungary

Toxalim UMR 1331 INRA/INP/UPS, Neuro-Gastroenterology & Nutrition Unit, Toulouse, France

Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary.

Reprints: Anita Annaházi, MD, First Department of Medicine, University of Szeged, Szeged. Koranyi fasor 8-10., 6720, Hungary (e-mail: annanita3@yahoocom).

The first two authors contributed equally to this work.

Anita Annaházi was a recipient of a postdoctoral fellowship from INRA. Supported by an institutional grant from INRA and TÁMOP (TÁMOP-4.2.1/B-09/1/KONV-2010-0005).

Received March 20, 2012

Accepted March 29, 2012

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