Majken Lindholm1,2, Antonio Di Sabatino3, Tina Manon-Jensen4, Giuseppe Mazza5, Gunvor I Madsen6, Paolo Giuffrida3, Massimo Pinzani5, Aleksander Krag7, Morten A Karsdal4, Jens Kjeldsen7, Joachim H Mortensen4. 1. Biomarkers and Research, Nordic Bioscience, Herlev hovedgade 205-207, 2730, Herlev, Denmark. mlo@nordicbio.com. 2. Department of Medical Gastroenterology, University of Southern Denmark and Odense University Hospital, Odense, Denmark. mlo@nordicbio.com. 3. First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy. 4. Biomarkers and Research, Nordic Bioscience, Herlev hovedgade 205-207, 2730, Herlev, Denmark. 5. Institute for Liver and Digestive Health, University College of London, London, UK. 6. Department of Surgical Pathology, Odense University Hospital, Odense, Denmark. 7. Department of Medical Gastroenterology, University of Southern Denmark and Odense University Hospital, Odense, Denmark.
Abstract
BACKGROUND: The laminin gamma 1 chain (LMγ1) is abundant along the crypt-villus axis in the intestinal basement membrane. AIMS: We investigated whether a serological biomarker of laminin degradation was associated with disease activity in patients with Crohn's disease (CD) and in rats with dextran sulfate sodium (DSS)-induced colitis. METHODS: Serum samples from CD patients (n = 43), healthy subjects (n = 19), and Sprague Dawley rats receiving 5-6% DSS water for five days and regular drinking water for 11 days were included in this study. The LG1M biomarker, a neo-epitope degradation fragment of the LMγ1 chain generated by matrix metalloproteinases-9 (MMP-9), was measured in serum to estimate the level of laminin degradation. RESULTS: Serum LG1M was elevated in CD patients with active and inactive disease compared to healthy subjects (p < 0.0001). LG1M distinguished CD patients from healthy subjects, with an area under the curve (AUC) of 0.81 (p < 0.0001). Serum LG1M was decreased in DSS rats compared to controls 2 days after DSS withdrawal, and increased upon reversal of the disease. CONCLUSIONS: Increased serum LG1M in active and inactive CD patients supports the evidence of altered LM expression in both inflamed and non-inflamed tissue. Moreover, lower LG1M levels in the early healing phase of DSS-induced colitis may reflect ongoing mucosal repair.
BACKGROUND: The laminin gamma 1 chain (LMγ1) is abundant along the crypt-villus axis in the intestinal basement membrane. AIMS: We investigated whether a serological biomarker of laminin degradation was associated with disease activity in patients with Crohn's disease (CD) and in rats with dextran sulfate sodium (DSS)-induced colitis. METHODS: Serum samples from CD patients (n = 43), healthy subjects (n = 19), and Sprague Dawley rats receiving 5-6% DSS water for five days and regular drinking water for 11 days were included in this study. The LG1M biomarker, a neo-epitope degradation fragment of the LMγ1 chain generated by matrix metalloproteinases-9 (MMP-9), was measured in serum to estimate the level of laminin degradation. RESULTS: Serum LG1M was elevated in CD patients with active and inactive disease compared to healthy subjects (p < 0.0001). LG1M distinguished CD patients from healthy subjects, with an area under the curve (AUC) of 0.81 (p < 0.0001). Serum LG1M was decreased in DSS rats compared to controls 2 days after DSS withdrawal, and increased upon reversal of the disease. CONCLUSIONS: Increased serum LG1M in active and inactive CD patients supports the evidence of altered LM expression in both inflamed and non-inflamed tissue. Moreover, lower LG1M levels in the early healing phase of DSS-induced colitis may reflect ongoing mucosal repair.
Authors: Joachim Høg Mortensen; Tina Manon-Jensen; Michael Dam Jensen; Per Hägglund; Lone Gabriels Klinge; Jens Kjeldsen; Aleksander Krag; Morten Asser Karsdal; Anne-Christine Bay-Jensen Journal: PLoS One Date: 2017-10-13 Impact factor: 3.240