Sepsis is the leading cause of morbidity and mortality in critically ill patients. The 30-day mortality in patients with severe sepsis is approximately 30%. In addition to excessive inflammatory response, unregulated apoptosis of peripheral circulating lymphocytes and splenocytes had been observed in patients with severe sepsis and may lead to immunosupression. However, the mechanism of lymphocyte apoptosis remains unclear. BCL3 gene encodes proteins which interact with p50 NF-kB homodimers and promote the survival of activated T-cell lymphocytes. We try to correlate the expression of BCL3 gene with the count of peripheral blood lymphocyte and other clinical variables.
We investigated the expression of BCL3 gene by RT-PCR method in patients with severe sepsis, which required ICU admission. We also analyzed peripheral lymphocyte count and clinical parameters, including age, sex, infection source、white blood cell count、APACHE II score、SOFA score、number of organ dysfunction、duration of shock and mechanical ventilation、need for dialysis、ICU and hospital stay、microbiology and 28-day mortality。Univariate and multivariate analyses are performed using gene expression and clinical variables.
A total of 51 patients with severe sepsis had been analyzed. Another 9 healthy people had been enrolled as control group. The mean BCL-3 gene expression (represented as 2-△CT BCL3-TBP) was 33.9 in septic group and 2.1 in control group (P=0.021). Lymphopenia was common on admission (75.5%) and subsided partially one week later (52.3%). The patients with higher BCL3 gene expression had shorter duration for recovery of peripheral blood lymphocytes.
Kaplan-Meier analysis revealed that higher BCL3 gene expression was associated with poor prognosis in 28-day mortality (38.7% vs. 10.0%, P=0.022). Statistical analysis showed patients with higher BCL3 gene expression had less 28-day survival time (22.0±9.2 vs. 27.1±3.2 days, P=0.022), higher SOFA score on ICU admission (10.2±3.4 vs. 8.2±2.3, P=0.022), more 28-day shock-free duration (14.5±12.0 vs. 22.2±9.2 days, P=0.021) than those with lower BCL3 expression. In Cox proportional hazards regression model, higher BCL3 gene expression, APACHE II score and ventilator-free day were independent prognostic factors for 28-day mortality, with a hazard ratio of 26.1 (95%CI, 1.547-440.3, P=0.024), 1.156 (95%CI, 1.029-1.298, P=0.014) and 0.865 (95%CI, 0.763 – 0.982, P=0.025) for 28-day mortality, respectively.
The study revealed that BCL3 gene expression was increased in the patients with severe sepsis. The patients with higher BCL-3 expression had shorter duration for the recovery of peripheral circulating lymphocytes, but it was correlated with poor short-term outcome.