Severe Altered Immune Status After Burn Injury Is Associated With Bacterial Infection and Septic Shock

Abstract

Introduction: Burn injury is associated with a high risk of death. Whether a pattern of immune and inflammatory responses after burn is associated with outcome is unknown. The aim of this study was to explore the association between systemic immune and inflammatory responses and outcome in severely-ill burn patients. Materials and Methods: Innate immunity, adaptive immunity, activation and stress and inflammation biomarkers were collected at admission and days 2, 7, 14, and 28 in severely-ill adult burn patients. Primary endpoint was mortality at day 90, secondary endpoint was secondary infections. Healthy donors (HD) served as controls. Multiple Factorial Analysis (MFA) was used to identify patterns of immune response. Results: 50 patients were included. Age was 49.2 (44.2-54.2) years, total burn body surface area was 38.0% (32.7-43.3). Burn injury showed an upregulation of adaptive immunity and activation biomarkers and a down regulation of innate immunity and stress/inflammation biomarkers. High interleukin-10 (IL-10) at admission was associated with risk of death. However, no cluster of immune/inflammatory biomarkers at early timepoints was associated with mortality. HLA-DR molecules on monocytes at admission were associated with bacterial infections and septic shock. Later altered immune/inflammatory responses in patients who died may had been driven by the development of septic shock. Conclusion: Burn injury induced an early and profound upregulation of adaptive immunity and activation biomarkers and a down regulation of innate immunity and stress/inflammation biomarkers. Immune and inflammatory responses were associated with bacterial infection and septic shock. Absence of immune recovery patterns was associated with poor prognosis.

Keywords: burns; immunosuppression; inflammation; intensive care; outcome; prognostic.

Figure 1

Multiple Factor Analysis (MFA). The analysis was based on 69 biomarkers and 76 individuals (healthy volunteers and burn patients at D0). (A) Healthy Donors (black dots) and burn patients (red dots) are presented as points on the scatter plot created with the first two main dimensions of Multiple Factorial Analysis (MFA). This analysis displayed the variability within the group of burn patients through dimension 1 (index of repartition: 0.54) whereas all controls are less spread in dimension 1 (controls: 0.75). (B) The correlation circle was generated using the most discriminating biomarkers between the two groups of individuals. The biomarkers were classified in four groups: activation markers (red), adaptive immunity markers (green), innate immunity markers (blue) and stress or inflammation markers (pink).

Figure 2

Comparative plots of the selected most discriminative biomarkers. Healthy donors (HD, filled circles) and burn patients at day 0 (D0, open circles) within the group of discriminative activation biomarkers (A). the group of discriminative innate biomarkers (B) and the group of discriminative stress and inflammation biomarkers (C).

Figure 3

Association between immune profiles and mortality. (A) Patterns of monocytes HLA-DR and serum cytokine levels between survivors (in gray) and non-survivors (in black) at day 90. Comparison of the number of HLA-DR molecules per monocyte (HLA-DR/monocytes), IL-10, IL-6, and IL-17 from day (D) 0 to D28 between burn patients who survived at day 90 or not. The number of patients is indicated below each plot. (B) Survivors (black dots) and non-survivors (red dots) at day 90 are presented in the first two dimensions of MFA of each four predefined subsets of immune markers. (C) Comparative trajectories from D0 to D7. Two classes of trajectories, red and black, were defined by k-means clustering. (D) Contingency table displaying patients with red or black trajectory depending on whether they survive at D90. *p < 0.05; ** p < 0.001.

Figure 4

Association between immune profiles, bacterial infection and septic shock. (A) Contingency table displaying patients with red or black trajectory (refer to Figure 3C), depending on whether develop bacterial infection. (B) Kinetic analysis of the number of HLA-DR molecules per monocyte (HLA-DR/monocytes) and cytokines between patients with (in black) or without septic shock (in gray). *p < 0.05; **p < 0.001.