Background and Study Aim: Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease characterized by remission of disease activity. Searching for laboratory markers which are simple, sensitive, specific and noninvasive is fundamental to assess the extent of inflammation, activity of the disease, evolution and prognosis which can be used to assess response to treatment and the possibility of relapse. Our aim of the work was to investigate the diagnostic role of fecal calprotectin and serum MMP-9 in determining the activity of ulcerative colitis. Patients and Methods: 71 patients were included in the study and fecal calprotectin, serum MMP-9, ESR and CRP were measured in these patients to determine the disease activity of ulcerative colitis. Results: Fecal calprotectin concentration in the patients with active UC was significantly higher than that in inactive disease and in controls (387.21 ± 44.07 μg/g vs 103.62 ± 119.67 μg/g, 12.44 ± 3.65 μg/g, p = 0.000). Serum MMP-9 was found to be higher in patients with active UC than in patients with inactive disease (11.02 ± 5.29 vs 4.01 ± 1.72 ng/ml, p = 0.000). A significant difference was also found in the patients with active UC of mild, moderate and severe degrees. Also, strong positive correlation was found between fecal calprotectin and serum MMP-9 and the severity of the disease. The area under the curve of the receiver operating characteristics (AUCROC) was 0.949 and 0.941 for fecal calprotectin and serum MMP-9 respectively. Conclusion: Fecal calprotectin and serum MMP-9 can be used to differentiate between active and inactive forms of UC.
Torres, J., Billioud, V., Sachar, D.B., Peyrin-Biroulet, L. and Colombel, J.-F. (2012) Ulcerative Colitis as a Progressive Disease: The Forgotten Evidence. Inflammatory Bowel Diseases, 18, 1356-1363. https://doi.org/10.1002/ibd.22839
Annese, V., Daperno, M., Rutter, M.D., et al. (2013) European Evidence Based Consensus for Endoscopy in Inflammatory Bowel Disease. Journal of Crohn’s and Colitis, 7, 982-1018. https://doi.org/10.1016/j.crohns.2013.09.016
Angriman, I., Scarpa, M., D’Inca, R., et al. (2007) Enzymes in Feces: Useful Markers of Chronic Inflammatory Bowel Disease. Clinica Chimica Acta, 381, 63-68. https://doi.org/10.1016/j.cca.2007.02.025
Schoepfer, A.M., Beglinger, C., Straumann, A., et al. (2009) Ulcerative Colitis: Correlation of the Rachmilewitz Endoscopic Activity Index with Fecal Calprotectin, Clinical Activity, C-Reactive Protein, and Blood Leukocytes. Inflammatory Bowel Diseases, 15, 1851-1858. https://doi.org/10.1002/ibd.20986
Travis, S.P., Schnell, D., Krzeski, P., et al. (2013) Reliability and Initial Validation of the Ulcerative Colitis Endoscopic Index of Severity. Gastroenterology, 145, 987-995. https://doi.org/10.1053/j.gastro.2013.07.024
Walsh, A.J., Ghosh, A., Brain, A.O., et al. (2014) Comparing Disease Activity Indices in Ulcerative Colitis. Journal of Crohn’s and Colitis, 8, 318-325. https://doi.org/10.1016/j.crohns.2013.09.010
Nikolaus, S. and Schreiber, S. (2007) Diagnostics of Inflammatory Bowel Disease. Gastroenterology, 133, 1670-1689. https://doi.org/10.1053/j.gastro.2007.09.001
Dubinsky, M.C., Ofman, J.J., Urman, M., Targan, S.R. and Seid-man, E.G. (2001) Clinical Utility of Serodiagnostic Testing in Suspected Pediatric Inflammatory Bowel Disease. American Journal of Gastroenterology, 96, 758-765. https://doi.org/10.1111/j.1572-0241.2001.03618.x
Desai, D., Faubion, W.A. and Sandborn, W.J. (2007) Review Article: Biological Activity Markers in Inflammatory Bowel Disease. Alimentary Pharmacology & Therapeutics, 25, 247-255. https://doi.org/10.1111/j.1365-2036.2006.03184.x
Tibble, J.A., Sigthorsson, G., Bridger, S., Fagerthol, M.K. and Bjarnason, I. (2000) Surrogate Markers of Intestinal Inflammation Are Predictive of Relapse in Patients with Inflammatory Bowel Disease. Gastroenterology, 119, 15-22. https://doi.org/10.1053/gast.2000.8523
Bitton, A., Peppercorn, M.A., Antonioli, D.A., et al. (2001) Clinical, Biological, and Histologic Parameters as Predictors of Relapse in Ulcerative Colitis. Gastroenterology, 120, 13-20. https://doi.org/10.1053/gast.2001.20912
Sutherland, A.D., Gearry, R.B. and Frizelle, F.A. (2008) Review of Fecal Biomarkers in Inflammatory Bowel Disease. Diseases of the Colon & Rectum, 51, 1283-1291. https://doi.org/10.1007/s10350-008-9310-8
Dale, I., Brandtzaeg, P., Fagerhol, M.K. and Scott, H. (1985) Distribution of a New Myelomonocytic Antigen (L1) in Human Peripheral Blood Leukocytes. Immunofluorescence and Immun-operoxidase Staining Features in Comparison with Lysozyme and Lactoferrin. American Journal of Clinical Pathology, 84, 24-34. https://doi.org/10.1093/ajcp/84.1.24
Roseth, A.G., Kristinsson, J., Fagerhol, M.K., Schjonsby, H., Aadland, E., Nygaard, K. and Roald, B. (1993) Faecal Calprotectin: A Novel Test for the Diagnosis of Colorectal Cancer? Scandinavian Journal of Gastroenterology, 28, 1073-1076. https://doi.org/10.3109/00365529309098312
Johne, B., Fagerhol, M.K., Lyberg, T., Prydz, H., Brandtzaeg, P., Naess-Andresen, C.F. and Dale, I. (1997) Functional and Clinical Aspects of the Myelomonocyte Protein Calprotectin. Molecular Pathology, 50, 113-123. https://doi.org/10.1136/mp.50.3.113
Roseth, A.G., Fagerhol, M.K., Aadland, E. and Schjonsby, H. (1992) Assessment of the Neutrophil Dominating Calprotectin in Feces: A Methodologic Study. Scandinavian Journal of Gastroenterology, 27, 793-798. https://doi.org/10.3109/00365529209011186
Egeblad, M. and Werb, Z. (2002) New Functions for the Matrix Metalloproteinases in Cancer Progression. Nature Reviews Cancer, 2, 161-174. https://doi.org/10.1053/gast.2000.8523
Santana, A., Medina, C., Paz-Cabrera, M.C., et al. (2006) Attenuation of Dextran Sodium Sulphate Induced Colitis in Matrix Metalloproteinase-9 Deficient Mice. World Journal of Gastroenterology, 12, 6464-6472. https://doi.org/10.3748/wjg.v12.i40.6464
Gan, X., Wong, B., Wright, S.D. and Cai, T.-Q. (2001) Production of Matrix Metalloproteinase-9 in CaCO-2 Cells in Response to Inflammatory Stimuli. Journal of Interferon & Cytokine Research, 21, 93-98. https://doi.org/10.1089/107999001750069953
Castaneda, F.E., Walia, B., Vijay-Kumar, M., et al. (2005) Targeted Deletion of Metalloproteinase 9 Attenuates Experimental Colitis in Mice: Central Role of Epithelial-Derived MMP. Gastroenterology, 129, 1991-2008. https://doi.org/10.1053/j.gastro.2005.09.017
Schroeder, K.W., Tremaine, W.J. and Ilstrup, D.M. (1987) Coated Oral 5-Aminosalicylic Acid Therapy for Mildly to Moderately Active Ulcerative Colitis: A Randomized Study. New England Journal of Medicine, 317, 1625-1629. https://doi.org/10.1056/NEJM198712243172603
Ordas, I., Eckmann, L., Talamini, M., Baumgart, D.C. and Sandborn, W.J. (2012) Ulcerative Colitis. The Lancet, 380, 1606-1619. https://doi.org/10.1016/S0140-6736(12)60150-0
Talley, N.J., Abreu, M.T., Achkar, J.P., et al. (2011) An Evidence-Based Systematic Review on Medical Therapies for Inflammatory Bowel Disease. The American Journal of Gastroenterology, 106, S2-S25. https://doi.org/10.1038/ajg.2011.58
Abraham, C. and Cho, J.H. (2009) Inflammatory Bowel Disease. New England Journal of Medicine, 361, 2066-2078. https://doi.org/10.1056/NEJMra0804647
Molodecky, N.A., Soon, I.S., Rabi, D.M., et al. (2012) Increasing Incidence and Prevalence of the Inflammatory Bowel Diseases with Time, Based on Systematic Review. Gastroenterology, 142, 46-54, e42. https://doi.org/10.1053/j.gastro.2011.10.001
Dignass, A., Eliakim, R., Magro, F., et al. (2012) Second European Evidence-Based Consensus on the Diagnosis and Management of Ulcerative Colitis Part 1: Definitions and Diagnosis. Journal of Croh’s and Colitis, 6, 965-990. https://doi.org/10.1016/j.crohns.2012.09.003
Bjerke, K., Halstensen, T.S., Jahnsen, F., Pulford, K. and Brandtzaeg, P. (1993) Distribution of Macrophages and Granulocytes Expressing L1 Protein (Calprotectin) in Human Peyer’s Patches Compared with Normal Ileal Lamina Propria and Mesenteric Lymph Nodes. Gut, 34, 1357-1363. https://doi.org/10.1136/gut.34.10.1357
Costa, F., Mumolo, M.G., Ceccarelli, L., et al. (2005) Calprotectin Is a Stronger Predictive Marker of Relapse in Ulcerative Colitis than in Crohn’s Disease. Gut, 54, 364-368. https://doi.org/10.1136/gut.2004.043406
Sands, B.E. (2015) Biomarkers of Inflammation in Inflammatory Bowel Disease. Gastroenterology, 149, 1275-1285. https://doi.org/10.1053/j.gastro.2015.07.003
Konikoff, M.R. and Denson, L.A. (2006) Role of Fecal Calprotectin as a Biomarker of Intestinal Inflammation in Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 12, 524-534. https://doi.org/10.1097/00054725-200606000-00013
Menees, S.B., Powell, C., Kurlander, J., Goel, A. and Chey, W.D. (2015) A Meta-Analysis of the Utility of C-Reactive Protein, Erythrocyte Sedimentation Rate, Fecal Calprotectin, and Fecal Lactoferrin to Exclude Inflammatory Bowel Disease in Adults with IBS. The American Journal of Gastroenterology, 110, 444-454. https://doi.org/10.1038/ajg.2015.6
Garcia-Sanchez, V., Iglesias-Flores, E., Gonzalez, R., et al. (2010) Does Fecal Calprotectin Predict Relapse in Patients with Crohn’s Disease and Ulcerative Colitis? Journal of Crohn’s and Colitis, 4, 144-152. https://doi.org/10.1016/j.crohns.2009.09.008
Tchetverikov, I., Lard, L.R., DeGroot, J., et al. (2003) Matrix Metalloproteinases-3, -8, -9 as Markers of Disease Activity and Joint Damage Progression in Early Rheumatoid Arthritis. Annals of the Rheumatic Diseases, 62, 1094-1099. https://doi.org/10.1136/ard.62.11.1094
Meijer, M.J.W., Mieremet-Ooms, M.A.C., van der Zon, A.M., et al. (2007) Increased Mucosal Matrix Metalloproteinase-1, -2, -3 and -9 Activity in Patients with Inflammatory Bowel Disease and the Relation with Crohn’s Disease Phenotype. Digestive and Liver Disease, 39, 733-739. https://doi.org/10.1016/j.dld.2007.05.010
Ravi, A., Garg, P. and Sitaraman, S.V. (2007) Matrix Metalloproteinases in Inflammatory Bowel Disease: Boon or a Bane? Inflammatory Bowel Diseases, 13, 97-107. https://doi.org/10.1002/ibd.20011
Xiang, J.Y., Ouyang, Q., Li, G.D. and Xiao, N.P. (2008) Clinical Value of Fecal Calprotectin in Determining Disease Activity of Ulcerative Colitis. World Journal of Gastroenterology, 14, 53-57.
Lakatos, G., Hritz, I., Varga, M.Z., et al. (2012) The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases. Digestive Diseases, 30, 289-295.
Matusiewicz, M., Neubauer, K., Mierzchala-Pasierb, M., Gamian, A. and Krzystek-Korpacka, M. (2014) Matrix Metalloproteinase-9: Its Interplay with Angiogenic Factors in Inflammatory Bowel Diseases. Disease Markers, 2014, Article ID: 643645.