Neutrophil Gelatinase B-associated Lipocalin and Matrix Metalloproteinase-9 Complex as a Surrogate Serum Marker of Mucosal Healing in Ulcerative Colitis

被引:50
作者
de Bruyn, Magali [1 ,2 ]
Arijs, Ingrid [2 ]
Wollants, Willem-Jan [2 ]
Machiels, Kathleen [2 ]
Van Steen, Kristel [3 ]
Van Assche, Gert [2 ]
Ferrante, Marc [2 ]
Rutgeerts, Paul [2 ]
Vermeire, Severine [2 ]
Opdenakker, Ghislain [1 ]
机构
[1] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Leuven, Belgium
[2] Katholieke Univ Leuven, Dept Clin & Expt Med, Translat Res Ctr Gastrointestinal Disorders TARGI, Leuven, Belgium
[3] Univ Liege, Inst Montefiore, B-4000 Liege, Belgium
关键词
NGAL-MMP-9; complex; ulcerative colitis; mucosal healing; surrogate serum marker; neutrophil; INFLAMMATORY-BOWEL-DISEASE; MATRIX METALLOPROTEINASES; INFLIXIMAB TREATMENT; FECAL CALPROTECTIN; CROHNS-DISEASE; NGAL; MMP-9; PROTEIN; EXPRESSION; BIOMARKERS;
D O I
10.1097/MIB.0000000000000068
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background:The current standard for the assessment of mucosal healing after therapy in inflammatory bowel diseases is endoscopy. However, a high need exists for noninvasive, accurate surrogate markers.Methods:In 2 independent cohorts, levels of serum neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 complex (NGAL-MMP-9) from patients with active ulcerative colitis (UC) before and after first treatment with infliximab and from healthy controls (HC) were determined with zymography and sandwich enzyme-linked immunosorbent assay. The response to infliximab was defined as complete mucosal healing (Mayo endoscopic subscore 0-1) at control endoscopy. Data were analyzed with SPSS, and P values <0.05 were considered significant.Results:In cohort 1 (n = 66; median age, 30 yr; 38% female), serum NGAL-MMP-9 levels significantly increased at baseline in UC patients versus HC (103.8 versus 42.4 ng/mL; P < 0.0001), whereas 55% of the patients had normal C-reactive protein levels. NGAL-MMP-9 levels significantly decreased after therapy in UC responders (from 116.3 ng/mL to 32.0 ng/mL; P < 0.0001) and in nonresponders (from 94.7 ng/mL to 54.1 ng/mL; P = 0.047). In cohort 2 (n = 132; median age, 39 yr; 53% female), NGAL-MMP-9 levels increased at baseline in active UC patients versus HC (86.5 versus 60.4 ng/mL; P = 0.10), whereas 45% of the patients had normal C-reactive protein levels. NGAL-MMP-9 levels significantly decreased after therapy in responders (from 87.5 ng/mL to 16.3 ng/mL; P < 0.0001) but not in nonresponders (from 82.7 ng/mL to 57.8 ng/mL; P = 0.19). After pooling the data, a cutoff value of 97.7 ng/mL for NGAL-MMP-9 complex was determined to predict complete mucosal healing with high specificity (91%).Conclusions:Serum NGAL-MMP-9 is suggested as a new surrogate marker for the assessment of mucosal healing in UC patients treated with infliximab.
引用
收藏
页码:1198 / 1207
页数:10
相关论文
共 35 条
[1]   Fecal MMP-9: A New Noninvasive Differential Diagnostic and Activity Marker in Ulcerative Colitis [J].
Annahazi, Anita ;
Molnar, Tamas ;
Farkas, Klaudia ;
Rosztoczy, Andras ;
Izbeki, Ferenc ;
Gecse, Krisztina ;
Inczefi, Orsolya ;
Nagy, Ferenc ;
Foeldesi, Imre ;
Szucs, Monika ;
Dabek, Marta ;
Ferrier, Laurent ;
Theodorou, Vassilia ;
Bueno, Lionel ;
Wittmann, Tibor ;
Roka, Richard .
INFLAMMATORY BOWEL DISEASES, 2013, 19 (02) :316-320
[2]   Mucosal Gene Expression of Antimicrobial Peptides in Inflammatory Bowel Disease Before and After First Infliximab Treatment [J].
Arijs, Ingrid ;
De Hertogh, Gert ;
Lemaire, Katleen ;
Quintens, Roel ;
Van Lommel, Leentje ;
Van Steen, Kristel ;
Leemans, Peter ;
Cleynen, Isabelle ;
Van Assche, Gert ;
Vermeire, Severine ;
Geboes, Karel ;
Schuit, Frans ;
Rutgeerts, Paul .
PLOS ONE, 2009, 4 (11)
[3]   Matrix metalloproteinase levels are elevated in inflammatory bowel disease [J].
Baugh, MD ;
Perry, MJ ;
Hollander, AP ;
Davies, DR ;
Cross, SS ;
Lobo, AJ ;
Taylor, CJ ;
Evans, GS .
GASTROENTEROLOGY, 1999, 117 (04) :814-822
[4]  
Biancheri A, 2011, DIFFERENTIAL CLEAVAG
[5]  
Bolignano D, 2010, J INVEST MED, V58, P569, DOI 10.231/JIM.0b013e3181ccc20c
[6]   Neutrophil gelatinase-associated lipocalin (NGAL) in human neoplasias: A new protein enters the scene [J].
Bolignano, Davide ;
Donato, Valentina ;
Lacquaniti, Antonio ;
Fazio, Maria Rosaria ;
Bono, Caterina ;
Coppolino, Giuseppe ;
Buemi, Michele .
CANCER LETTERS, 2010, 288 (01) :10-16
[7]   Neutrophils, from Marrow to Microbes [J].
Borregaard, Niels .
IMMUNITY, 2010, 33 (05) :657-670
[8]   Lipocalin 2 Is Required for Pulmonary Host Defense against Klebsiella Infection [J].
Chan, Yvonne R. ;
Liu, Jessica S. ;
Pociask, Derek A. ;
Zheng, Mingquan ;
Mietzner, Timothy A. ;
Berger, Thorsten ;
Mak, Tak W. ;
Clifton, Matthew C. ;
Strong, Roland. K. ;
Ray, Prabir ;
Kolls, Jay K. .
JOURNAL OF IMMUNOLOGY, 2009, 182 (08) :4947-4956
[9]   Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease [J].
D'Haens, Geert ;
Ferrante, Marc ;
Vermeire, Severine ;
Baert, Filip ;
Noman, Maja ;
Moortgat, Liesbeth ;
Geens, Patricia ;
Iwens, Doreen ;
Aerden, Isolde ;
Van Assche, Gert ;
Van Olmen, Gust ;
Rutgeerts, Paul .
INFLAMMATORY BOWEL DISEASES, 2012, 18 (12) :2218-2224
[10]   Analysis of gelatinases in complex biological fluids and tissue extracts [J].
Descamps, FJ ;
Martens, E ;
Opdenakker, G .
LABORATORY INVESTIGATION, 2002, 82 (11) :1607-1608