Abstract
Acute pancreatitis (AP) is a painful and potentially life-threatening disorder with the potential for therapeutic interventions. Biomarkers that characterize cases by severity and pathogenic mechanisms involved are not yet available but needed for the implementation of rational therapies. Here, we used shotgun proteomics to obtain information from plasma samples about local and systemic pathologies taking place during cases of alcoholic AP. Plasma was obtained at Kaunas University of Medicine Hospital (Lithuania) from 12 AP patients of alcohol related etiology (median age of 40) within 24 h of presentation, and 12 age-matched, healthy controls. Patients entered into the study had moderately severe AP with the following characteristics: mean blood lactate dehydrogenase level of 1127 mg/dl; median APACHEII score of 5.5 and mean IMRIE score of 3.5. For proteomic analysis, less-abundant proteins in plasma samples were enriched using Top 12 abundant protein depletion columns. Further processing was performed by a modified filter-assisted sample preparation combined with tandem mass tag labeling for quantitation. Samples were analyzed using an Orbitrap Elite mass spectrometer for high resolution liquid chromatography–tandem mass spectrometry (LC–MS/MS). Our analysis revealed 31 proteins that exhibited significant 1.5-fold or higher increases in the AP compared to control patients, and six that were significantly decreased. Gene ontology analysis indicated a strong correlation with exosomal origin in the elevated proteins, with 29/31 (93.5%) associated with this extracellularly-secreted compartment. Elevated proteins included established and proposed biomarkers of AP including C-reactive protein, LPS-binding protein, intercellular adhesion molecule-1, and von Willebrand factor, as well as several novel potential biomarkers. These results provide the methodology for proteomic analysis of plasma samples to discover novel biomarkers that characterize pancreatitis cases by pathogenic mechanism as well as disease activity at an early stage that is highly informative for routine clinical practice and clinical trials.
Highlights
Acute pancreatitis is one of the most common diseases of the gastrointestinal tract, leading to tremendous emotional, physical, and financial human burden (Papachristou et al, 2010)
Selected Acute pancreatitis (AP) patients were all males with alcohol as potential etiologic factor
Given the wide range of outcomes in AP, and the failure of clinical scoring systems to adequately prepare caregivers for different outcomes in the AP disease course, much research has been dedicated to identification of stand-alone protein biomarkers which would be of value in assessing the severity of AP patients
Summary
Acute pancreatitis is one of the most common diseases of the gastrointestinal tract, leading to tremendous emotional, physical, and financial human burden (Papachristou et al, 2010). Alcohol does not cause pancreatitis by itself but increases the susceptibility to pancreatitis by affecting pancreatic physiology at multiple levels, of which the most important is its ability to sensitize the pancreas to other insults (Aframian et al, 1996; Pandol et al, 1999). One such cofactor is smoking, which can increase the risk of pancreatitis independently (Andriulli et al, 2010; Greer et al, 2015). Genetic susceptibility can explain an increased risk of pancreatitis in some individuals who drink
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