Increased Levels of Histone in Human Plasma in Septic Patients with DIC

<Background and Methods>

Sepsis is a life-threatening condition that is characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome, SIRS). Histones are essential for packing DNA into the cell nucleus and also play role in regulating gene expression but the new study (Jun Xu et al, Nature Medicine 15. 1318, 2009) have shown histones released into blood stream at the onset of sepsis can have devastating effects (endothelial damage and organ failure etc). However, plasma levels of histone are unclear in septic patients with DIC. Therefore, We developed a sandwich ELISA to quantify serum or plasma histone H3 levels and measured plasma levels of histone H3 in septic patients with DIC (n=30).

<Results>

DIC was diagnosed on the Japanese Ministry of Health and Welfare (JMHW) DIC diagnostic criteria. The thrombin antithrombin complexes (TAT) levels were higher in septic patients with DIC as reported by others. The working range of this ELISA was 3-1000 ng/ml. In healthy volunteers, plasma levels of histone (H3) were not detectable. We detected high levels of extracellular hisotone (H3) in the plasma of all septic patients with DIC by sandwich ELISA. Mean plasma levels of hisotone (H3) were 70.5 ± 63.2 (12.9-336.5) ng/ml in septic patients with DIC. However, plasma levels of extracellular histone (H3) were negative in acute promyelocytic leukemia (APL)-induced DIC (n=5). Also, Plasma levels of histone were 10 ng/ml or less by sandwich ELISA in septic patients without DIC (n=8).

<Conclusion>

These results suggest that assess of extracellular hisotones in the plasma may be helpful in the making the diagnosis in septic patients with DIC. Also, it appears that extracellular hisotones in the plasma may contribute to develop DIC in septic patients.