Integrated systems biology of multiple organ dysfunction in acute pancreatitis

Acute pancreatitis (AP) is an inflammatory condition of the pancreas. Main identified causes are gallstones and alcohol abusive consumption. It can lead, in 20% of the cases, to multiple organ dysfunction syndrome (MODS) requiring the admission to an intensive care unit and causing death in approximately 20% of the cases. At the time there is no specific therapy to treat AP or to prevent AP-MODS. Care currently provided to patients with AP is solely supportive and thus constitutes a crucial need to address.

Recently, an enzyme (Kynurenine-3-monooxygenase), part of the kynurenine pathway and involved in tryptophan metabolism, has been identified as playing a key role in AP-MODS. On mice with no KMO activity, when AP was induced, lungs, liver and kidneys were protected from being damaged. In this context an inhibitor of KMO has been developed and is aimed at producing a similar effect on patients with AP.

Currently, there is no way of predicting MODS during AP, thus it is not possible to predict which patients could actually benefit from this new therapeutic strategy. In this context, seventy-nine patients presenting AP were recruited from the Royal Infirmary of Edinburgh. For this cohort, metabolomics profiling, RNA-sequencing and clinical data collection were performed at different time points using blood samples.

This comprehensive dataset could be used to try to stratify the cohort in order to identify subgroups that could benefit from the new potential medicine as well as identifying shared features that could help in understanding AP biology better. Outcome prediction is also important to perform as it has the potential to help anticipating MODS. Therapeutic targets could as well be identified using data-analysis methods and find relevant elements that could be investigated further as treatment targets.