Th125 - Neutrophil Inflammation and Platelet Activation Underlie Organ Failure in Acute Pancreatitis

Abstract Text: Acute Pancreatitis (AP) is an enigmatic disorder caused by autodigestion of the pancreas, which can either result in a mild self-limiting form or can progress to a severe form characterized by distant organ failure which carries a high rate of mortality. There is relatively limited data describing the immunology of acute pancreatitis, and thus, significant interest given that this is a highly inflammatory condition. In this study we employed longitudinal whole blood RNA sequencing and matched complete blood count panels following hospitalization to determine the molecular signatures which differentiate mild versus severe AP. Participants with more severe AP demonstrated elevated transcriptional signatures of neutrophil-driven inflammation and platelet activation which mirrors clinical findings. In contrast, participants with mild AP demonstrated higher expression of B and T lymphocyte genes, indicating an innate versus adaptive immune axis in the progression or resolution of AP. While most immune-related processes return to baseline quickly, a subset of megakaryocyte genes remain elevated in severe cases revealing a new potential route of interrogation to understand severe complications post-AP. Finally, by employing complementary machine learning-based approaches we confirm that transcriptional networks enriched for neutrophil-mediated inflammation are a hallmark of more severe disease. Together, our data indicates that neutrophil driven inflammation and coagulopathy may underlie the spread of damage from the pancreas to other organs, which presents a potential opportunity for better predicting patient risk and devising new treatment options.