Role of Plasma DNA as a Predictive Marker of Fatal Outcome following Severe Head Injury in Males

Abstract

The prediction of outcome is one of the major problems associated with traumatic brain injury. Recently, investigations have been performed on the potential use of circulating cell-free DNA in plasma for clinical diagnosis and prognosis of a variety of conditions. In this study, we investigated DNA plasma concentrations after severe traumatic brain injury (TBI) and its correlation with primary outcome. We studied 41 male victims of TBI, with isolated severe TBI or severe TBI with associated exracranial injuries. Control samples were obtained from 13 healthy male volunteers. Plasma DNA was measured by a real-time PCR assay for the beta-globin gene. The mean time for first sampling (study entry) was 11.7 +/- 5.2 h after injury; subsequent DNA determinations were performed 24 h after study entry. Mean plasma DNA concentrations were significantly increased in TBI patients (366,485 and 131,708 kilogenomes-equivalents/L, at study entry and 24 h later, respectively) compared with the control group (3031 kilogenomes-equivalents/L). Additionally, a significant correlation between higher plasma DNA concentrations, determined 24 h after study entry, and fatal outcome was observed. However, at second sampling, there was no significant correlation between plasma DNA concentrations and the presence of associated extracranial injuries. High plasma DNA concentrations at second sampling time predicted fatal outcome with a sensitivity of 67% and specificity of 76%, considering a cut-off value of 77,883 kilogenomes-equivalents/L. Thus, this study showed that severe TBI is associated with elevated DNA plasma levels and suggests that persistent DNA elevations correlate with mortality.

Elevated Cell-Free Plasma DNA Level as an Independent Predictor of Mortality in Patients with Severe Traumatic Brain Injury

“…22 In the present study, we enrolled a larger sample of patients with severe TBI (either isolated severe TBI or TBI associated with extracerebral lesions) from both sexes and determined plasma cell-free DNA concentrations at ICU admission, within 12 h after trauma. In addition, we analyzed the association between plasma cell-free DNA levels and hospital admission GCS scores.…”

“…In contrast with previous studies, in the present study, a single determination early after the trauma (mean 6 h) predicted fatal outcome of the patients with severe TBI admitted to the ICU. 22,27 Temporal profile post-injury may influence assessment of the predictive value of plasma cell-free DNA after severe TBI. Accordingly, Lo and coworkers 49 reported in a study investigating healthy pregnant women that DNA has a rapid clearance from plasma, with a mean estimated half-life of 16.3 min (range 4-30 min).…”

“…40,41 A previous study of our group showed that severe TBI is associated with elevated DNA plasma levels and suggested that persistent DNA elevations correlated with mortality. 22 Recently, Macher and associates 27 investigated plasma DNA in 65 patients after severe TBI in the first 96 h after ICU admission. After an initial peak, a higher decrease was detected within the first 24 h among survivors compared with non-survivors.…”

“…22,37,40,41,45 The precise mechanism by which DNA is released into the bloodstream remains uncertain, because both necrosis and apoptosis have been observed in this scenario. 46 Further, decreased efficiency of DNA clearance mechanisms after injury may play a role in the increase of cell-free DNA in trauma.…”

The Duality of AIM2 Inflammasome: A Focus on its Role in Autoimmunity and Skin Diseases

“…For example, it has been shown that AIM2 is implicated in inflammation and cell death of the brain. Cerebrospinal Fluid (CSF) of patients with traumatic brain injury often contains cell-free DNA fragments rather than the CSF from non-trauma patients and this correlates with mortality (Adamczak et al, 2014;Campello Yurgel et al, 2007). Adamczak and colleagues have demonstrated that human embryonal cortical neurons express functional AIM2 inflammasome, they release IL-1β and they undergo pyroptosis upon AIM2 activation with poly (dA:dT) transfection.…”