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

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Abstract

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 re-analysed 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.

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