Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis
Marianna Miliaraki, Panagiotis Briassoulis, Stavroula Ilia, Aikaterini Polonifi, Marina Mantzourani, Efrossini Briassouli, Konstantinos Vardas, Serafim Nanas, Aikaterini Pistiki, Μαρία Θεοδωρακοπούλου, T. Tavladaki, Anna Maria Spanaki, Εumorfia Kondili, Helen Dimitriou, Sotirios Tsiodras, Dimitrios Georgopoulos, Apostolos Armaganidis, George L. Daikos, George Briassoulis
Abstract
Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.