307 The Association Between Immune Dysfunction and Outcome of Septic Patients: A Prospective Observational Study

Abstract

Sepsis is a dysregulated host response to an infection or injury which features as a multiple-system failure. Immune mechanism plays a vital role in the pathogenesis of sepsis. Some immune status might exist in septic patients, such as systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and mixed antagonistic response syndrome (MARS), which is a severe imbalance of pro- and anti-inflammatory activities. The objective of this study is to explore the association between prognosis of sepsis and immune markers, namely pro-inflammatory markers such as tumor necrosis factor (TNF)-α, interleukin (IL)-2R, IL-6, IL-8, and anti-inflammatory markers such as IL-10, CD14+ monocyte human leukocyte antigen-D related (HLA-DR) expression. Also, the prognosis of each immune status was also targeted. A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between October 2016 and December 2018. Peripheral blood samples of patients were collected at day 1, day 3 and day 7 after admission. Medical records were screened for available clinical data. Plasma cytokines level were measured by enzyme-linked immunosorbent assay (ELISA) method and the flow cytometry was performed to measure the CD14+ monocyte HLA-DR expression. The median value of each immune marker was used as the cut-off point. Level of a pro-inflammatory marker higher than cut-point was marked as (+) , so was an anti-inflammatory marker lower than cut-point. Otherwise, it was marked as (-). Immune status of sepsis was classified according to levels of immune markers. SIRS was defined as 0-4 pro-inflammatory markers(+) and 0 anti-inflammatory markers(+). CARS was defined as 0-2 pro-inflammatory markers(+) and 1-2 anti-inflammatory marker(+). MARS was defined as 3-4 pro-inflammatory markers(+) and 1-2 anti-inflammatory marker(+). We analyzed the association between in-hospital mortality of septic patients and immune markers, as well as three immune status. Statistical analysis was conducted on SPSS 25.0 A total of 174 septic patients were enrolled in the study, among whom 124 survived and 50 did not. Immune markers were significantly associated with outcomes of sepsis (TNF-α: P<0.01 at day 1, P<0.001 at day 3; IL-2R: P=0.013 at day 1, P=0.029 at day 3; IL-6: P<0.001 at day 1 and day 3;IL-8:P<0.001 at day1 and day 3, P=0.023; IL-10: P<0.001 at day1 and day 3,P=0.006 at day 7; HLA-DR expression: P<0.001 at day1 and day 3). MARS caused higher in-hospital mortality than SIRS and CARS (P<0.001). Survival analysis also revealed that patients with MARS had poor 30-day survival than patients with SIRS and CARS (Log-rank test: P<0.001). Immune markers such as plasma cytokines level and CD14+ monocyte HLA-DR expression were associated with prognosis of septic patients. Patients with severe immune disorder, defined as MARS, could be predictive of poor outcome.