Circulating cyclophilin A levels elevate in animal models and can predict mortality in patients with acute pancreatitis.

Abstract

Background/objectives: Cyclophilin A (CypA) is released into the blood following cellular injury and correlates with acute pancreatitis (AP) severity, however, investigations into circulating CypA in experimental AP and hypertriglyceridaemia-associated AP (HTG-AP) prevalent cohorts are lacking.

Methods: C57Bl/6 mice received 4, 8, and 12 caerulein injections to induce escalating severity of AP models (CER-AP). Mice were sacrificed 1 h after the last injection of caerulein to assess severity of CER-AP through biochemical and histopathological analyses, and serum CypA levels were also measured. Golden Syrian hamsters fed with a high-cholesterol/high-fat diet were given 10 caerulein injections to induce experimental HTG-AP to assess severity and serum CypA. Human blood plasma samples taken within 24 h after admission from a patient cohort with a predominance of HTG-AP cases, stored in a prospectively collected AP Biobank, were assessed for plasma CypA levels and correlated with clinical data.

Results: In mice, CER-AP models showed significantly increased pancreatic histopathological scores and biochemical parameters, with severity highest after 12 caerulein injections. Serum CypA levels were significantly higher in all CER-AP models compared to controls. In hamsters, CypA levels were significantly higher in HTG-AP model than controls. In AP patients, CypA levels in non-haemolytic plasma samples varied by aetiology, with the highest levels in HTG-AP, corresponding to HTG levels and AP severity. ROC analysis revealed CypA ≥9.9 ng/ml as a significant predictor of mortality (AUC = 0.865).

Conclusion: Circulating CypA levels are significantly increased in mouse CER-AP and hamster HTG-AP models. We have identified a novel association of raised plasma CypA levels with severity of HTG-AP and confirmed its significant prognostic ability to predict mortality in AP patients.