Pancreatic and Duodenal Secretion Proteomic Profiling in Severe Acute Pancreatitis: 2011 ACG Presidential Poster

Abstract

Purpose: Acute pancreatitis (AP) is an inflammatory disease of the pancreas, which evolves in approximately 20% of the patients to a severe illness associated with a high mortality rate. But so far, there is no good way to identify the severity and prognosis of AP. In this study, we performed a comparative proteomic analysis of pancreatic and duodenal secretion from human subjects with AP and healthy controls in order to identify changes in protein expression related to the pathobiological processes of this disease. Methods: Pancreatic and duodenal secretion from 5 AP patients and 5 healthy volunteers matched with age, sex and BMI were stimulated by polymeric enteral feeding. 120 minutes after stimulation, the sample was collected through enteral feeding tube, and then analyzed by isotope-coded affinity tags (ICATs) and tandem mass spectrometry method. Briefly: Proteins from different samples were labeled with isotopically heavy (with 8 deuterium) and light (no deuterium) ICAT reagents, respectively, for quantitative analysis. Two-dimensional LC separation, including SCX and RP-LC, was applied for fractionation of the samples before Mass spectrometry analysis. Results: Total 241 proteins were identified, of which 96 proteins showed abundance increase and 15 proteins decrease at least two-fold in samples from AP compared to that from healthy volunteers, some of them being newly described in AP (Table). As anticipated, pancreatic enzymes were down-regulated. In addition, we observed increased expression of various inflammatory markers, including several members of the alpha-macroglobulin family. We also detected changes related to oxidative and cell stress responses. Conclusion: Proteomic analysis has the capacity to identify key regulators of the pathophysiologic mechanisms responsible for acute pancreatitis. Further functional studies are needed to determine the role these proteins play in injury and recovery.Figure: No Caption available.