Campello Yurgel Virginia, Ikuta Nilo, Brondani da Rocha Adriana, Lunge Vagner Ricardo, Fett Schneider Rogerio, Kazantzi Fonseca André Salvador, Grivicich Ivana, Zanoni Caroline, Regner Andrea
Programa de Pós-Graduação em Diagnóstico Genético e Molecular, Universidade Luterana do Brasil, Canoas, Brazil.
J Neurotrauma. 2007 Jul;24(7):1172-81. doi: 10.1089/neu.2006.0160.
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.
创伤性脑损伤结局的预测是与之相关的主要问题之一。近来，人们对血浆中循环游离DNA在多种疾病临床诊断和预后评估中的潜在用途进行了研究。在本研究中，我们调查了重度创伤性脑损伤（TBI）后的血浆DNA浓度及其与主要结局的相关性。我们研究了41名男性TBI受害者，他们要么是单纯性重度TBI，要么是伴有颅外损伤的重度TBI。对照样本取自13名健康男性志愿者。采用针对β-珠蛋白基因的实时PCR检测法测定血浆DNA。首次采样（研究入组）的平均时间为受伤后11.7±5.2小时；在研究入组24小时后进行后续的DNA测定。与对照组（3031千基因组当量/L）相比，TBI患者的平均血浆DNA浓度显著升高（研究入组时和24小时后分别为366,485和131,708千基因组当量/L）。此外，在研究入组24小时后测定的较高血浆DNA浓度与致命结局之间存在显著相关性。然而，在第二次采样时，血浆DNA浓度与伴有颅外损伤的情况之间没有显著相关性。以77,883千基因组当量/L为临界值，第二次采样时高血浆DNA浓度预测致命结局的敏感性为67%，特异性为76%。因此，本研究表明重度TBI与血浆DNA水平升高有关，并提示持续的DNA升高与死亡率相关。
