Magali de Bruyn1, Ingrid Arijs2, Gert De Hertogh3, Marc Ferrante2, Gert Van Assche2, Paul Rutgeerts2, Séverine Vermeire2, Ghislain Opdenakker4. 1. Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Translational Research Center for Gastrointestinal Disorders [TARGID], Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. 2. Translational Research Center for Gastrointestinal Disorders [TARGID], Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium. 3. Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. 4. Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium ghislain.opdenakker@rega.kuleuven.be.
Abstract
BACKGROUND AND AIMS: Although costly and uncomfortable for the patient, the current standard to assess mucosal healing in Crohn's disease [CD] patients is endoscopy. The aim of this study was to evaluate NGAL-MMP-9 as surrogate marker for mucosal healing in CD patients. METHODS: Serum NGAL-MMP-9 levels were determined with sandwich enzyme-linked immunosorbent assay before and up to 5 years after first infliximab infusion in 108 active CD patients [median age at first infliximab 36 years, 57% female] and 43 healthy controls [HC, median age 27 years, 60% female]. Serum samples were matched to the time of endoscopy and complete endoscopic healing was defined as absence of ulcerations. Histological healing was defined as absence of epithelial damage [D'Haens score]. RESULTS: At baseline, median [interquartile range] NGAL-MMP-9 levels were significantly higher in active CD patients vs HC (77.6 [36.9-141.0] vs 25.5 [17.8-42.8] ng/ml; p < 0.001). After treatment, NGAL-MMP-9 levels significantly decreased in completely healed CD patients [n = 38] (84.5 [36.7-138.4] to 23.4 [7.4-42.5] ng/ml; p < 0.001) and--to a lesser extent--in non-healed CD patients [n = 36] (100.9 [43.4-152.6] to 43.8 [27.0-96.8] ng/ml; p = 0.001). Receiver operating characteristic analysis defined a NGAL-MMP-9 cut-off level of 45 ng/ml corresponding to complete endoscopic healing (area under the curve [AUC] = 0.79, 82% sensitivity, 65% specificity) and histological healing [AUC = 0.72, 79% sensitivity, 53% specificity]. At baseline, C-reactive protein [CRP] was not elevated in 33% of active CD patients, whereas 53% of these patients did have elevated NGAL-MMP-9 levels. CONCLUSIONS: In the search for surrogate markers to assess mucosal healing in inflammatory bowel disease, NGAL-MMP-9 supplements and outperforms CRP in both ulcerative colitis and CD patients.
BACKGROUND AND AIMS: Although costly and uncomfortable for the patient, the current standard to assess mucosal healing in Crohn's disease [CD] patients is endoscopy. The aim of this study was to evaluate NGAL-MMP-9 as surrogate marker for mucosal healing in CDpatients. METHODS: Serum NGAL-MMP-9 levels were determined with sandwich enzyme-linked immunosorbent assay before and up to 5 years after first infliximab infusion in 108 active CDpatients [median age at first infliximab 36 years, 57% female] and 43 healthy controls [HC, median age 27 years, 60% female]. Serum samples were matched to the time of endoscopy and complete endoscopic healing was defined as absence of ulcerations. Histological healing was defined as absence of epithelial damage [D'Haens score]. RESULTS: At baseline, median [interquartile range] NGAL-MMP-9 levels were significantly higher in active CDpatients vs HC (77.6 [36.9-141.0] vs 25.5 [17.8-42.8] ng/ml; p < 0.001). After treatment, NGAL-MMP-9 levels significantly decreased in completely healed CDpatients [n = 38] (84.5 [36.7-138.4] to 23.4 [7.4-42.5] ng/ml; p < 0.001) and--to a lesser extent--in non-healed CDpatients [n = 36] (100.9 [43.4-152.6] to 43.8 [27.0-96.8] ng/ml; p = 0.001). Receiver operating characteristic analysis defined a NGAL-MMP-9 cut-off level of 45 ng/ml corresponding to complete endoscopic healing (area under the curve [AUC] = 0.79, 82% sensitivity, 65% specificity) and histological healing [AUC = 0.72, 79% sensitivity, 53% specificity]. At baseline, C-reactive protein [CRP] was not elevated in 33% of active CDpatients, whereas 53% of these patients did have elevated NGAL-MMP-9 levels. CONCLUSIONS: In the search for surrogate markers to assess mucosal healing in inflammatory bowel disease, NGAL-MMP-9 supplements and outperforms CRP in both ulcerative colitis and CDpatients.
Authors: Magali de Bruyn; Christine Breynaert; Ingrid Arijs; Gert De Hertogh; Karel Geboes; Greet Thijs; Gianluca Matteoli; Jialiang Hu; Jo Van Damme; Bernd Arnold; Marc Ferrante; Séverine Vermeire; Gert Van Assche; Ghislain Opdenakker Journal: Nat Commun Date: 2017-05-31 Impact factor: 14.919
Authors: Silje Thorsvik; Ingunn Bakke; Atle van Beelen Granlund; Elin Synnøve Røyset; Jan Kristian Damås; Ann Elisabet Østvik; Arne Kristian Sandvik Journal: Cell Tissue Res Date: 2018-06-05 Impact factor: 5.249
Authors: Bram Verstockt; Sare Verstockt; Jonas Dehairs; Vera Ballet; Helene Blevi; Willem-Jan Wollants; Christine Breynaert; Gert Van Assche; Séverine Vermeire; Marc Ferrante Journal: EBioMedicine Date: 2019-01-24 Impact factor: 8.143
Authors: Wouter T van Haaften; Joachim H Mortensen; Anders K Dige; Henning Grønbæk; Christian L Hvas; Anne-Christine Bay-Jensen; Morten A Karsdal; Peter Olinga; Tina Manon-Jensen; Gerard Dijkstra Journal: Clin Transl Gastroenterol Date: 2020-09 Impact factor: 4.396