Integrated systems biology of multiple organ dysfunction in acute pancreatitis

急性胰腺炎（AP）是胰腺的一种炎症。主要确定的原因是胆结石和酗酒。在20%的病例中，它可导致多器官功能障碍综合征（MODS），需要入住重症监护病房，并导致约20%的病例死亡。当时还没有专门的治疗AP或预防AP- mods的方法。目前向AP患者提供的护理完全是支持性的，因此构成了一个至关重要的需求。最近，一种犬尿氨酸-3-单加氧酶（kynurenine -3-monooxygenase）作为犬尿氨酸途径的一部分，参与色氨酸代谢，被发现在AP-MODS中起关键作用。在没有KMO活性的小鼠上，AP诱导时，肺、肝和肾均不受损伤。在此背景下，一种KMO抑制剂已经被开发出来，旨在对AP患者产生类似的效果。目前，没有办法预测AP期间的MODS，因此无法预测哪些患者实际上可以从这种新的治疗策略中受益。在此背景下，从爱丁堡皇家医院招募了79名AP患者。在该队列中，使用血液样本在不同时间点进行代谢组学分析、rna测序和临床数据收集。这个全面的数据集可以用来尝试对队列进行分层，以确定可以从新的潜在药物中受益的亚组，以及确定可以帮助更好地理解AP生物学的共同特征。结果预测也很重要，因为它有可能帮助预测MODS。也可以使用数据分析方法确定治疗靶点，并找到可以作为治疗靶点进一步研究的相关元素。

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.