P088 Serum Matrix Metalloproteinase-3 Concentration Correlates with Clinical and Endoscopic Evidence of Ulcerative Colitis
K. Kawashima*1, S. Ishihara1, H. Sonoyama1, Y. Tada1, A. Oka1, R. Kusunoki1, N. Fukuba1, N. Oshima1, I. Moriyama1, T. Yuki2, Y. Kinoshita1
1Shimane University School of Medicine, Internal Medicine II, Izumo, Japan, 2Shimane University Hospital, Gastrointestinal Endoscopy, Izumo, Japan
Matrix metalloproteinase-3 (MMP-3), a 59-kDa protein and one of 4 known stromelysins among MMPs, has been reported to be up-regulated in inflamed areas in ulcerative colitis (UC) and is considered to play an important role in mucosal injury. However, the levels of MMP-3 in UC patient serum and its clinical effects remain unknown. We examined whether serum MMP-3 levels are correlated with clinical and endoscopic evidence of UC.
This study was prospectively conducted from February 2013 to April 2014 at 2 hospitals in Japan. Patients with a history of colorectal surgery and coexisting collagen disease were excluded. Serum samples were collected at the first visit during the study period and serum MMP-3 was assessed in relation to the clinical activity index (CAI) of Rachmilwitz, defined as 5 or more active phases, as previously reported. Serum MMP-3 level was also measured on the day or within 1 week of a complete colonoscopy procedure, with those patients scored according to Mayo endoscopic subscore (MES), with scores of 2 and 3 used to denote an active phase. We then assessed the correlation of serum MMP-3 with MES.
One hundred thirteen patients with UC (mean age 47.6 ± 18.5 years; 65 males, 48 females) were enrolled in the study. Mean serum MMP-3 level was significantly higher in the active (n=22, 155.6 ± 22.2 ng/ml) as compared to inactive (n=91, 58.4 ± 5.0 ng/ml) phase (p<0.001) and significantly correlated with CAI (Spearman's rank correlation coefficient r=0.43, p<0.001). A complete colonoscopy was performed 110 times in 89 patients during the study period. In those, median serum MMP-3 for MES 0 (n=26), 1 (n=46), 2 (n=28), and 3 (n=10), was 45.5 ng/ml (range 12-108 ng/ml), 55.0 ng/ml (17-456 ng/ml), 88.4 ng/ml (24-367 ng/ml), and 127 ng/ml (50-388 ng/ml), respectively. That level in MES 2 and 3 cases was significantly elevated as compared to both MES 0 and 1, though that in MES 1 was not significantly elevated as compared to MES 0 cases. Serum MMP-3 levels showed a significant correlation with MES (r=0.45, p<0.001). For detection of endoscopic evidence in males, serum MMP-3 levels with a cutoff of 92.4 ng/ml had a sensitivity of 69% and a specificity of 82% (MES 2-3), while in females with a cutoff of 36.7 ng/ml those were 83% and 74%, respectively.
Our Results showed that serum MMP-3 levels are elevated during active phases of UC and have a significant correlation with colonoscopic findings. Thus, MMP-3 may be useful as a clinical biomarker in UC patients.