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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

Citation

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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.
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.
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.
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.
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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