Scavengers of hemoproteins as potential biomarkers for severe sepsis and septic shock

Abstract

Abstract Background Despite improvements in diagnosis, interventions and supportive care, mortality among sepsis patients is still high. Research of the past decade has attempted to identify biomarkers that can accurately discriminate sepsis from other diseases with comparable symptoms to improve diagnosis, but results have been lackluster. Recent studies have shown that hemoproteins and damage-associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA) released as the result of hemolysis play an important role in the pathogenesis of sepsis. The aim of this study was to measure plasma levels of the indirect markers for hemoproteins hemopexin, haptoglobin and heme oxygenase-1 (HO-1) as well as the mitochondrial damage marker mtDNA in the plasma of a cohort of sepsis patients to determine the feasibility of their use as biomarkers in the diagnosis of sepsis. Methods Hemopexin, haptoglobin and HO-1 were measured in plasma by ELISA and mtDNA was measured by digital droplet PCR. Plasma levels of hemopexin, haptoglobin, HO-1 and mtDNA were measured in 32 patients with severe sepsis and 8 patients with septic shock at baseline and 4 days after admission to the ICU and in 20 healthy donors. Results Plasma levels of hemopexin were significantly lower and plasma levels of HO-1, haptoglobin and mtDNA were significantly higher in patients with severe sepsis and septic shock at baseline compared to healthy controls. Additionally, HO-1 levels were significantly higher in patients with septic shock compared to patients with severe sepsis. Finally, levels of HO-1 and mtDNA, but not of hemopexin, seemed to slowly revert back towards levels measured in healthy donors within 5 days after admission. Conclusions Our results indicate that plasma levels of the hemoprotein scavengers hemopexin, haptoglobin and HO-1 and the mitochondrial damage marker mtDNA might be useful as additional biomarkers for the early diagnosis of sepsis and disease severity.