Genetics, Cell Biology, and Pathophysiology of Pancreatitis

Gastroenterology. 2019 May;156(7):1951-1968.e1. doi: 10.1053/j.gastro.2018.11.081. Epub 2019 Jan 18.


Since the discovery of the first trypsinogen mutation in families with hereditary pancreatitis, pancreatic genetics has made rapid progress. The identification of mutations in genes involved in the digestive protease-antiprotease pathway has lent additional support to the notion that pancreatitis is a disease of autodigestion. Clinical and experimental observations have provided compelling evidence that premature intrapancreatic activation of digestive proteases is critical in pancreatitis onset. However, disease course and severity are mostly governed by inflammatory cells that drive local and systemic immune responses. In this article, we review the genetics, cell biology, and immunology of pancreatitis with a focus on protease activation pathways and other early events.

Keywords: Cell Death; Genetics; Inflammation; Pancreatitis; Trypsinogen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Enzyme Activation
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation Mediators / metabolism
  • Mutation
  • Necrosis
  • Pancreas* / enzymology
  • Pancreas* / immunology
  • Pancreas* / pathology
  • Pancreas* / physiopathology
  • Pancreatitis* / enzymology
  • Pancreatitis* / genetics
  • Pancreatitis* / pathology
  • Pancreatitis* / physiopathology
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism
  • Phenotype
  • Prognosis
  • Protein Folding
  • Risk Factors
  • Signal Transduction


  • Inflammation Mediators
  • Peptide Hydrolases