Figure 1
HMGB1 is released with Plasmodium falciparum infection and predictive of malarial disease severity and clinical outcome in Ugandan children. Plasma HMGB1 levels at clinical presentation are significantly higher in children with severe malaria (SM) compared to uncomplicated malaria (UM) (A) and in fatal cases when compared to non-fatal cases (B). Statistical analysis by Mann Whitney U test. * indicates a p value of <0.01. (C) Receiver operating characteristics (ROC) curves were generated for HMGB1 (solid line) and parasitaemia (dashed line) to assess the utility in predicting outcome. Area under the curve (AUC) is displayed with 95% confidence intervals in parentheses. p values were adjusted for multiple comparisons using Bonferroni-Holm’s correction (n = 2). * indicates a significant p value of <0.025 (D) HMGB1 is detectable in cultured media 24 hours following peripheral blood mononuclear cells (PBMC; 1.5 × 106 per well) (isolated from healthy, malaria-naïve donors) stimulation with parasitized erythrocytes PEs (4.5 × 106 per well) or LPS (100 ng/ml) but not after stimulation with uninfected erythrocytes (uE; 4.5 × 106 per well) or media alone. HMGB1 was analysed by western blot using rabbit polyclonal anti-HMGB1 antibodies. (E) The kinetics of HMGB1 release from PBMCs (1.5 × 106 per well) was assessed two, six and 24 hours after stimulated with PEs (4.5 × 106 per well) or LPS (100 ng/ml).