| Abstract |
Background: Sepsis and systematic inflammatory response syndrome (SIRS) of varying aetiology are common in critically ill patients. Sepsis is characterized by an abnormal systematic immunologi-cal response to an infectious pathogen, which may progress to multi-organ dysfunction, and thus it can be life-threatening. It has been shown that apoptosis plays a crucial role during sepsis, especially concerning various cells of the immune system. Survivin belongs to the protein family of the Inhibi-tors of Apoptosis (IAP) and is pivotal in the regulation of cell mitosis and programmed cell death. It has been studied extensively in cancer and autoimmune diseases but not in sepsis.
Aim of the study: To identify the pattern of survivin expression and production in the clinical con-text of traumatic SIRS and sepsis, compare the two groups and correlate the results with various la-boratory and clinical markers of severity of sepsis.
Materials and methods: This study is part of a larger multicenter study (SIBIGHAM) which includes patients with sepsis according to the most recent definition of sepsis (sepsis-3) and patients with SIRS due to trauma. We performed measurements in samples of a representative part of these sub-jects: 18 patients with sepsis, 18 patients with SIRS and 9 healthy subjects (control). We performed survivin mRNA extraction from peripheral blood, quantitative assessment with a fluorescent dye, cDNA synthesis, and quantification with real-time PCR using a standard curve. Furthermore, we per-formed sandwich ELISA to assess serum survivin levels. Finally we made the statistical analysis by using statistical package SPSS 24.
Results: Comparing healthy individuals with the SIRS group, the transcriptional expression of sur-vivin isoforms in SIRS group revealed that survivin-total was significantly higher in the SIRS group (0,02±0,004 vs 0,003±0,001 ng/κl, p=0,022), while the other isoforms 2B, ΔEx3 and WT showed an augmentative trend. Serum survivin was increased in SIRS (233±45 pg/ml vs 125±45 pg/ml) (p=0,022). At the comparisons between healthy individuals and patients with sepsis, survivin-2B and survivin-ΔΓx3 were higher in sepsis group in comparison with healthy subjects (26,78±5,3 vs 3,57±0,8 ng/κl, p=0,028 and 0,295±0,254 vs 0,005±0,002, p=0,026 respectively), while survivin-3B was at the same levels as in control group, and survivin-WT tended to be higher (p>0,05). Serum survivin was increased in sepsis (438±151 pg/ml) versus control (125±45 pg/ml) (p=0,008). When the SIRS group was compared with the sepsis group, isoforms 2Β, ΔΓx3 and WT had an augmentative trend in sepsis, while isoforms survivin-total and 3B and serum survivin had a similar trend in SIRS (p>0,05). Correlations between survivin and clinical severity scores and laboratory measurements did not produce a significant pattern, in spite of some separate significant results.
Conclusions: Survivin is expressed and produced more intensely in the context of sepsis and trau-ma, in comparison with healthy individuals. The transcriptional expression levels of survivin isoforms 2B, ΔΓx3, WT and total, was diverse among the studied groups.
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