HMGB1 as a predictor of organ dysfunction and outcome in patients with severe sepsis

Objective: To study the predictive value of high mobility group box-1 protein ( HMGB1) and hospital mortality in adult patients with severe sepsis. Study design: Prospective observational cohort study in 24 ICUs in Finland. Patients: Two hundred and forty-seven adult patients with severe sepsis. Measurements and main results: Blood samples for HMGB1 analyses were drawn from 247 patients at baseline and from 210 patients 72 h later. The mean APACHE II and SAPS II scores were 24 ( SD 9) and 44 ( SD 17), respectively. The hospital mortality was 26%. The serum HMGB1 concentrations were measured first by semi-quantitative Western immunoblotting ( WB) analysis. The median HMGB1 concentration on day 0 was 108% ( IQR 98.5-119) and after 72 h 107% ( IQR 98.8-120), which differed from healthy controls ( 97.5%, IQR 91.3-106.5; p = 0.028 and 0.019, respectively). The samples were reanalysed by ELISA ( in a subgroup of 170 patients) to confirm the results by WB. The median concentration in healthy controls was 0.65 ng/ml ( IQR 0.51-1.0). This was lower than in patients with severe sepsis ( 3.6 ng/ml, IQR 1.9-6.5, p < 0.001). HMGB1 concentrations ( WB and ELISA) did not differ between hospital survivors and non-survivors. In ROC analyses for HMGB1 levels ( WB) on day 0 and 72 h with respect to hospital mortality, the areas under the curve were 0.51 and 0.56 ( 95% CI 0.40-0.61 and 0.47-0.65). Conclusions: Serum HMGB1 concentrations were elevated in patients with severe sepsis, but did not differ between survivors and non-survivors and did not predict hospital mortality.