5th Annual BMRP Investigator Meeting - Abstract
Fecal S100A12: A non-Invasive Stool Marker Released from Inflamed Mucosa during Active Inflammatory Bowel Disease
Dirk Foell1,a, Jost Langhorst3*, Zhigang Ren4, Helmut Wittkowski1,2, Tom Borody5, Robert Clancy4 and Johannes Roth1,2
1Department of Pediatrics, University of Muenster (Germany); 2Interdisciplinary Center of Clinical Research, University of Muenster (Germany); 3Department of Internal Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen (Germany); 4Hunter Immunology Unit, Hunter New England Area Health Service, John Hunter Hospital (Newcastle, NSW, Australia) and 5Centre for Digestive Diseases (Five Dock, NSW, Australia)
Phagocyte-derived S100 proteins have pro-inflammatory properties and may serve as biomarkers for disease activity. S100A12 is a neutrophil activation marker, while S100A8/S100A9 (MRP8/14, calprotectin) is less specific and also expressed in monocytes and possibly epithelial cells. We performed the first study analyzing fecal S100A12 in adults with signs of intestinal inflammation, correlating our results with findings in endoscopy and histology. Fecal S100A12 was significantly higher in patients with active IBD (2.45 ±1.15 mg/kg) compared to healthy controls (0.006 ±0.03 mg/kg; p <0.001) or patients with IBS (0.05 ±0.11 mg/kg; p <0.001). Fecal S100A12 distinguished active IBD from healthy controls and from IBS. We found an increased spontaneous release of S100A12 from tissue in IBD compared to IBS and healthy controls (p<0.0001). The release of S100A12 into the supernatants was 30-fold enhanced in inflamed tissue when compared to non-inflamed tissue (mean 9.35 ng/ml vs. 0.3 ng/ml, p<0.0001). This is the first demonstration of direct release of phagocyte-derived S100 proteins from local tissues under inflammatory conditions, which may reflect secretion from infiltrating neutrophils during active disease. This release correlates to endoscopic assessment of activity and validates the correlation of fecal S100 levels with disease activity in IBD.
aPrincipal Investigator