Prognostic value of plasma level of high mobility group box-1 in sepsis and septic shock

Abstract

Background: Although recent studies have suggested that plasma level of high mobility group box-1 (HMGB1), a pro-inflammatory damage associated molecular pattern (DAMP), may be associated with mortality of sepsis, the results are contradictory. Moreover, the relationship between HMGB1 and necroptosis, a programmed cell necrosis mechanism, is not known.

Objectives: The aim of this study was to analyze the association between plasma level of HMGB1 and sepsis severity and outcomes. Furthermore, the plasma level of HMGB1 was compared to that of RIPK3, a key executor of necroptosis, to identify any correlation between HMGB1 and necroptosis.

Methods: This was a prospective observation study on consecutive critically-ill patients admitted to the medical intensive care unit of Samsung Medical Center between 2014 and 2016. HMGB1 and RIPK3 was measured from plasma by ELISA.

Results: Of 188 critically ill patients, 58 (30.9%) and 84 (44.7%) patients were diagnosed with sepsis and septic shock, respectively. A statistically significant trend of increased plasma level of HMGB1 across the groups of control, sepsis, and septic shock was observed (2.4 ng/mL vs. 3.1 ng/mL vs. 5.7 ng/mL, P < 0.001). For 142 patients with sepsis, the group with high plasma HMGB1 was more likely to have septic shock and higher severity of illness scores. In addition, higher 28-day, in-hospital, and 90-day mortalities were observed in the high HMGB1 group. There was a strong correlation between plasma level of HMGB1 and RIPK3 (R2 = 0.6516, P < 0.001).

Method: Plasma level of HMGB1 was associated with severity and outcomes of sepsis. Plasma level of HMGB1 was correlated with plasma level of RIPK3.