ORIGINAL ARTICLE Fecal MMP-9: A New Noninvasive Differential Diagnostic and Activity Marker in Ulcerative Colitis Anita Annah  azi, MD,* ,† Tam as Moln  ar, MD, PhD,* Klaudia Farkas, MD, PhD,* Andr  as Roszt  oczy, MD, PhD,* Ferenc Izb eki, MD, PhD,* Krisztina Gecse, MD, PhD,* Orsolya Inczefi, MD,* Ferenc Nagy, MD, PhD,* Imre F € oldesi, PhD,* M onika Szu † cs, MSc, ‡ Marta Dabek, PhD, † Laurent Ferrier, PhD, † Vassilia Theodorou, PhD, † Lionel Bueno, PhD, † Tibor Wittmann, MD, PhD,* and Rich  ard R  oka, MD, PhD* 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 pre- dictor 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 diar- rhea (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 ¼ 47), IBS-D (n ¼ 23) patients, and control subjects (n ¼ 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 signifi- cantly correlated with the overall Mayo score (P < 0.001), the endoscopic score (P < 0.001), and the serum C-reactive protein levels (P ¼ 0.002). Additionally, in UC patients fecal MMP-9 levels showed a significant correlation with a known disease activity marker, fecal calprotectin (P ¼ 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. (Inflamm Bowel Dis 2012;000:000–000) Key Words: ulcerative colitis, MMP-9, disease activity score, calprotectin U lcerative colitis (UC) is a chronic, relapsing inflamma- tory bowel disease (IBD) characterized by continuous colonic mucosal ulceration and diarrhea during relapses. The differentiation of UC from functional disorders such as diarrhea predominant irritable bowel syndrome (IBS-D) is clinically challenging, as symptoms may include altered bowel habits and abdominal pain in both diseases and ac- tivity signs can mix with anxiety-driven symptoms as well in UC. Several attempts have been made to establish non- invasive markers that can clearly distinguish IBD from functional disorders and reveal strong correlation not only with clinical activity, but also with the endoscopic picture of the mucosa in UC. Among biochemical laboratory markers serum C-reactive protein (CRP) is the most stud- ied 1 ; however, while the activity of Crohn’s disease (CD) is accompanied by a strong CRP response in most patients, relapses in UC are characterized by only a modest or absent CRP increase, 2 depending mostly on the extension of the involved area; the sensitivity of CRP in the detection of UC is only 50%–70%. 3–5 The pathogenesis of UC includes the complex dysre- gulation of mucosal immune cells 6 accompanied by the invasion of neutrophils, which leads to the formation of crypt abscesses and to the dysfunction of the colonic epi- thelial barrier. 7 During transmigration, neutrophils reach the colonic lumen and can be detected in the stool, 8 similar Received for publication March 20, 2012; Accepted March 29, 2012. From the *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. The first two authors contributed equally to this work. Anita Annah azi was a recipient of a postdoctoral fellowship from INRA. Supported by an institutional grant from INRA and TA ´ MOP (TA ´ MOP-4.2.1/B- 09/1/KONV-2010-0005). Reprints: Anita Annah azi, MD, First Department of Medicine, University of Szeged, Szeged. Kor anyi fasor 8-10., 6720, Hungary (e-mail: annanita3@yahoo. com.). Copyright V C 2012 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.22996 Published online in Wiley Online Library (wileyonlinelibrary. com). Inflamm Bowel Dis 1