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Neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 complex as a surrogate serum marker of mucosal healing in ulcerative colitis

M de Bruyn, I Arijs, WJ Wollants, K Machiels, Kristel Van Steen (UGent) , G Van Assche, M Ferrante, P Rutgeerts, S Vermeire and G Opdenakker
(2014) INFLAMMATORY BOWEL DISEASES. 20(7). p.1198-1207
Author
Organization
Abstract
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.
Keywords
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

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MLA
de Bruyn, M., et al. “Neutrophil Gelatinase B-Associated Lipocalin and Matrix Metalloproteinase-9 Complex as a Surrogate Serum Marker of Mucosal Healing in Ulcerative Colitis.” INFLAMMATORY BOWEL DISEASES, vol. 20, no. 7, 2014, pp. 1198–207, doi:10.1097/MIB.0000000000000068.
APA
de Bruyn, M., Arijs, I., Wollants, W., Machiels, K., Van Steen, K., Van Assche, G., … Opdenakker, G. (2014). Neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 complex as a surrogate serum marker of mucosal healing in ulcerative colitis. INFLAMMATORY BOWEL DISEASES, 20(7), 1198–1207. https://doi.org/10.1097/MIB.0000000000000068
Chicago author-date
Bruyn, M de, I Arijs, WJ Wollants, K Machiels, Kristel Van Steen, G Van Assche, M Ferrante, P Rutgeerts, S Vermeire, and G Opdenakker. 2014. “Neutrophil Gelatinase B-Associated Lipocalin and Matrix Metalloproteinase-9 Complex as a Surrogate Serum Marker of Mucosal Healing in Ulcerative Colitis.” INFLAMMATORY BOWEL DISEASES 20 (7): 1198–1207. https://doi.org/10.1097/MIB.0000000000000068.
Chicago author-date (all authors)
de Bruyn, M, I Arijs, WJ Wollants, K Machiels, Kristel Van Steen, G Van Assche, M Ferrante, P Rutgeerts, S Vermeire, and G Opdenakker. 2014. “Neutrophil Gelatinase B-Associated Lipocalin and Matrix Metalloproteinase-9 Complex as a Surrogate Serum Marker of Mucosal Healing in Ulcerative Colitis.” INFLAMMATORY BOWEL DISEASES 20 (7): 1198–1207. doi:10.1097/MIB.0000000000000068.
Vancouver
1.
de Bruyn M, Arijs I, Wollants W, Machiels K, Van Steen K, Van Assche G, et al. Neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 complex as a surrogate serum marker of mucosal healing in ulcerative colitis. INFLAMMATORY BOWEL DISEASES. 2014;20(7):1198–207.
IEEE
[1]
M. de Bruyn et al., “Neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 complex as a surrogate serum marker of mucosal healing in ulcerative colitis,” INFLAMMATORY BOWEL DISEASES, vol. 20, no. 7, pp. 1198–1207, 2014.
@article{5905729,
  abstract     = {{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.}},
  author       = {{de Bruyn, M and Arijs, I and Wollants, WJ and Machiels, K and Van Steen, Kristel and Van Assche, G and Ferrante, M and Rutgeerts, P and Vermeire, S and Opdenakker, G}},
  issn         = {{1078-0998}},
  journal      = {{INFLAMMATORY BOWEL DISEASES}},
  keywords     = {{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}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1198--1207}},
  title        = {{Neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 complex as a surrogate serum marker of mucosal healing in ulcerative colitis}},
  url          = {{http://dx.doi.org/10.1097/MIB.0000000000000068}},
  volume       = {{20}},
  year         = {{2014}},
}
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