Comparison of fecal pyruvate kinase isoform M2 and calprotectin in assessment of pediatric inflammatory bowel disease severity and activity
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Aims: Accurate assessment of inflammatory bowel disease (IBD) activity is the cornerstone of effective therapy. Fecal M2 isoform of pyruvate kinase (M2-PK) and fecal calprotectin (FC) are noninvasive markers of mucosal inflammation in IBD. The aim of this study was to compare performance of M2-PK and FC in assessment of pediatric ulcerative colitis (UC) and Crohn's disease (CD) severity and activity. Materials and methods: 121 patients with IBD, including 75 with UC and 46 with CD were recruited. Control group consisted of 35 healthy children (HS). Patients were assigned to groups depending on disease severity and activity. M2-PK and calprotectin concentration were determined in stool samples using ELISA. Areas under receiver operating characteristic curves (AUC) for FC and M2-PK with cut-off level at which M2-PK specificity was matching FC specificity were calculated and compared. Results: Performance of M2-PK at identifying patients with IBD, UC and CD among HS was inferior to FC. The differences in AUC were respectively: -0.10 (95% confidence interval [CI] [-0.13-(-0.06)], p<0.0001), -0.14 (95% CI [-0.19-(-0.09)], p<0.0001) and -0.03 (95% CI [-0.05-(-0.001)], p<0.02). M2-PK was inferior to FC in discriminating patients with mild UC from those with HS (AUC difference -0.23, 95% CI [-0.31-(-0.15)], p<0.0001). Conclusions: FC reflects pediatric IBD severity and activity better than M2-PK. This difference is particularly pronounced when identifying patients with mild UC and UC in remission.
- Aomatsu T, Yoden A, Matsumoto K, Kimura E, Inoue K, Andoh A, Tamai H (2011) Fecal calprotectin is a useful marker for disease activity in pediatric patients with inflammatory bowel disease. Dig Dis Sci 56: 2372-2377.
- Bunn SK, Bisset WM, Main MJ, Golden BE (2001) Fecal calprotectin as a measure of disease activity in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr 32: 171-177.
- Czub E, Herzig KH, Szaflarska-Popawska A, Kiehne K, Socha P, Woś H, Kaminska B, Błaszczynski M, Cichy W, Bała G, Brodzicki J, Grzybowska-Chlebowczyk U, Walkowiak J (2007) Fecal pyruvate kinase: a potential new marker for intestinal inflammation in children with inflammatory bowel disease. Scand J Gastroenterol 42: 1147-1150.
- D'Haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L, Geens P, Iwens D, Aerden I, Van Assche G, Van Olmen G, Rutgeerts P (2012) Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 18: 2218-2224.
- Gupta V, Bamezai RN (2010) Human pyruvate kinase M2: a multifunctional protein. Protein Sci 19: 2031-2044.
- Henderson P, Anderson NH, Wilson DC (2013) The Diagnostic Accuracy of Fecal Calprotectin During the Investigation of Suspected Pediatric Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Am J Gastroenterol (online ahead of print).
- Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM, Kirschner BS, Griffiths AM, Katz AJ, Grand RJ, Boyle JT (1991) Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr 12: 439-447.
- Kallel L, Fekih M, Boubaker J, Filali A (2011) [Faecal calprotectin in inflammatory bowel diseases: review.] Tunis Med 89: 425-429.
- Kobelska-Dubiel N, Ignyś I, Cichy W, Kobelski M (2007) Clinical indices in inflammatory bowel diseases in children. Pediatria Współczesna. Gastroenterologia, Hepatologia i Żywienie Dziecka 9: 167-171.
- Komraus M, Wos H, Wiecek S, Kajor M, Grzybowska-Chlebowczyk U (2012) Usefulness of faecal calprotectin measurement in children with various types of inflammatory bowel disease. Mediators Inflamm 2012: 608249.
- Kornbluth A, Sachar DB, Practice Parameters Committee of the American College of Gastroenterology (2004) Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 99: 1371-1385.
- Kostakis ID, Cholidou KG, Vaiopoulos AG, Vlachos IS, Perrea D, Vaos G (2013) Fecal calprotectin in pediatric inflammatory bowel disease: a systematic review. Dig Dis Sci 58: 309-319.
- Lasson A, Simrén M, Stotzer PO, Isaksson S, Ohman L, Strid H (2013) Fecal calprotectin levels predict the clinical course in patients with new onset of ulcerative colitis. Inflamm Bowel Dis 19: 576-581.
- Mahadevan U, Loftus EV Jr, Tremaine WJ, Pemberton JH, Harmsen WS, Schleck CD, Zinsmeister AR, Sandborn WJ (2002) Azathioprine or 6-mercaptopurine before colectomy for ulcerative colitis is not associated with increased postoperative complications. Inflamm Bowel Dis 8: 311-316.
- Mao R, Xiao Y, Gao X, Chen B, He Y, Yang L, Hu P, Chen M (2012) Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflamm Bowel Dis 18: 1894-1899.
- Önal İK, Beyazit Y, Şener B, Savuk B, Özer Etık D, Sayilir A, Öztaş E, Torun S, Özderın Özın Y, Tunç Demırel B, Ülker A, Dağli Ü (2012) The value of fecal calprotectin as a marker of intestinal inflammation in patients with ulcerative colitis. Turk J Gastroenterol 23: 509-514.
- Shaoul R, Sladek M, Turner D, Paeregaard A, Veres G, Wauters GV, Escher J, Dias JA, Lionetti P, Staino A, Kolho KL, de Ridder L, Nuti F, Cucchiara S, Sheva O, Levine A, ESPGHAN Porto IBD Group (2012) Limitations of fecal calprotectin at diagnosis in untreated pediatric Crohn's disease. Inflamm Bowel Dis 18: 1493-1497.
- Shastri YM, Povse N, Schröder O, Stein J (2008) Comparison of a novel fecal marker--fecal tumor pyruvate kinase type M2 (M2-PK) with fecal calprotectin in patients with inflammatory bowel disease: a prospective study. Clin Lab 54: 389-390.
- Turner D, Leach ST, Mack D, Uusoue K, McLernon R, Hyams J, Leleiko N, Walters TD, Crandall W, Markowitz J, Otley AR, Griffiths AM, Day AS (2010) Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response. Gut 59: 1207-1212.
- Turner D, Otley AR, Mack D, Hyams J, de Bruijne J, Uusoue K, Walters TD, Zachos M, Mamula P, Beaton DE, Steinhart AH, Griffiths AM (2007) Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 133: 423-432.
- Van Assche G, Dignass A, Panes J, Beaugerie L, Karagiannis J, Allez M, Ochsenkühn T, Orchard T, Rogler G, Louis E, Kupcinskas L, Mantzaris G, Travis S, Stange E, European Crohn's and Colitis Organisation (ECCO) (2010) The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Definitions and diagnosis. J Crohns Colitis 4: 7-27.
- Van Rheenen PF, Van de Vijver E, Fidler V (2010) Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 341: c3369-c3369.
- Walkowiak J, Banasiewicz T, Krokowicz P, Hansdorfer-Korzon R, Drews M, Herzig KH (2005) Fecal pyruvate kinase (M2-PK): a new predictor for inflammation and severity of pouchitis. Scand J Gastroenterol 40: 1493-1494.
- Yui S, Nakatani Y, Mikami M (2003) Calprotectin (S100A8/S100A9), an inflammatory protein complex from neutrophils with a broad apoptosis-inducing activity. Biol Pharm Bull 26: 753-760.
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