Prognostic value of plasma exosomal levels of histone H3 protein in patients with heat stroke

Heat stroke (HS) is a condition that can lead to multiple organ dysfunction syndrome and death; however, there is no reliable method for stratifying mortality risk in HS. The abundance of exosomes in the circulation and their contents may be used as potential biomarkers of HS. The present study aimed to examine whether histone H3 levels in plasma exosomes could be used to determine HS prognosis. Blood samples were collected from patients with HS (36 survivors and 8 non-survivors) at admission to the intensive care unit and 4 days after admission. Blood samples were additionally collected from 15 healthy volunteers. Plasma exosomes were isolated using high-speed differential centrifugation. Correlation between histone H3 level and organ function and disease severity was examined. The results suggested differential expression and enrichment of histone H3 in the plasma exosomes of patients with HS (survivors, 249.3±04.6; non-survivors, 500.4±216.8; healthy controls, 161.1±52.49 pg/100 µg; P<0.05). The increased expression of histone H3 was associated with increased disease severity and duration. Plasma exosomal levels of histone H3 were significantly correlated with both organ dysfunction and disease severity (P<0.0001) and were significantly different between non-survivors and survivors (area under the receiver operating characteristic curve, 0.9668). A cutoff value of 307 pg/100 µg demonstrated optimized sensitivity (95%) and specificity (91.67%) for predicting mortality risk, suggesting that histone H3 levels in plasma exosomes may be a reliable biomarker for HS prognosis.