Circulating Levels of Peroxiredoxin 4 as a Novel Biomarker of Oxidative Stress in Patients with Sepsis

Abstract

Oxidative stress, a situation with increased reactive oxygen species production and/or decreased antioxidant defense mechanisms, is evident in the pathogenesis of sepsis. Peroxiredoxin 4 (Prx4) is a hydrogen peroxide degrading peroxidase recently found circulating in blood of septic patients and potentially reflecting an antioxidant system in imbalance. We studied Prx4 serum levels of 79 consecutively enrolled medical intensive care unit patients. The diagnostic and prognostic performance of Prx4 was compared with other biomarkers, the APACHE II score and the SOFA score. Median Prx4 serum levels gradually increased with disease severity in patients classified on admission as having systemic immune response syndrome (2.32 arbitrary [arb.] U/L), sepsis (5.02 arb. U/L), severe sepsis (11.7 arb. U/L), or septic shock (11.4 arb. U/L). A positive correlation was found with the severity score Acute Physiological and Chronic Health Evaluation II (r = 0.27, P < 0.05) and the organ failure score Sequential Organ Failure Assessment (r = 0.55, P < 0.0001). Peroxiredoxin 4 correlated with the sepsis marker procalcitonin (r = 0.61, P < 0.0001), the inflammatory markers C-reactive protein (r = 0.65, P < 0.0001) and interleukin 6 (r = 0.62, P < 0.0001), and antioxidant blood compounds total bilirubin (r = 0.37, P < 0.001) and albumin (r = -0.54, P < 0.0001). Peroxiredoxin 4 distinguished noninfectious from infectious inflammatory response syndrome with an area under the receiver operating characteristic (ROC) curve of 0.82. [corrected] High Prx4 serum levels were associated with a poor prognosis of septic patients and revealed an area under the ROC curve of 0.76 in prediction of in-hospital mortality. In this study, elevated serum levels of the antioxidant Prx4 were associated with an increased disease severity and adverse outcome of critically ill patients with sepsis. Peroxiredoxin 4 may therefore be a helpful new biomarker for diagnosing, monitoring, and risk assessing these patients. The pathophysiological mechanisms behind the observed increase remain to be elucidated.

Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain injury outcome

“…Our current model is further supported by findings that another peroxiredoxin, Prdx4, (the only known secretory member of the peroxiredoxin superfamily) was suggested as a “novel biomarker of oxidative stress in patients with “sepsis shock” [31] and this may be an indication of the general involvement of the peroxiredoxins in diseases that are linked with the “compartmentalized” antioxidant protection. Our discovery of Prdx6 in CSF fits well with this concept; however, the actual mechanism of how this enzyme is trafficked in CSF remains unclear.…”

Novel links among peroxiredoxins, endothelial dysfunction, and severity of atherosclerosis in type 2 diabetic patients with peripheral atherosclerotic disease

“…P<0.05 is statistically significant HbA 1c glycosylated hemoglobin, HOMA IR insulin resistance index, ESR erythrocyte sedimentation rate, ICAM-1 cellular adhesion molecule-1, VCAM-1 vascular cellular adhesion molecule-1, ND non-detectable, NS non-significant members of the peroxiredoxin family and demonstrated that circulating levels of PRDX1, 2, 4, and 6 are markedly raised in diabetic patients with PAD. Although little is known about the pathophysiological role of peroxiredoxins, there is an evidence that they are upregulated in conditions of increased ROS generation (Bast et al 2002;Schulte et al 2011), which supports our observation. Previous reports showed that exposure of cells to oxidative stress and heat shock induced chaperone function of PRDXs, in order to enhance cellular resistance to stressful stimuli (Jang et al 2004).…”

“…It is a hydrogen peroxide degrading peroxidase recently found circulating in blood of septic patients and potentially reflecting an antioxidant system in imbalance (Schulte et al 2011), similar to atherosclerosis (Madamanchi et al 2005). The amount of secreted PRDX4 is most likely proportional to the initial intracellular expression levels (Okado-Matsumoto et al 2000).…”

Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in nonobese diabetic mice

“…Peroxiredoxin 4 is a major anti-oxidative enzyme in the peroxiredoxin family, which has been used as an oxidative stress biomarker in chronic diseases such as cancers [53, 54]. In line with increased SOD production, both catalase and peroxiredoxin 4 were increased in the ileum of MO offspring.…”