From the Departments of *Anesthesiology, Emergency and Intensive Care Medicine, †Thoracic and Cardiovascular Surgery, ‡General and Visceral Surgery, §Medical Statistics, and ∥Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.
J Investig Med. 2014 Mar;62(3):638-43. doi: 10.2310/JIM.0000000000000059.
Sepsis is a life-threatening condition. Programmed cell death 1 protein (PD-1), a negative costimulatory molecule, is suggested to be involved in pathogenesis as mortality is associated with high expression and as neutralizing antibodies improve survival in a mouse model. The PD-1 gene harbors an intronic single-nucleotide polymorphism, rs11568821, which is located in a transcription factor-binding site and supposed to affect PD-1 transcription.
This study aimed at investigating whether mortality (90-day) among patients with sepsis associates with PD-1 rs11568821 genotypes.
Adult white patients with sepsis from the surgical intensive care units of a university medical center were followed up for 90 days, and mortality was recorded as primary outcome variable. Blood samples were taken for PD-1 rs11568821 genotyping. Sequential Organ Failure Assessment scores increased at enrollment and during the observation period to monitor morbidity.
Two hundred nineteen critically ill patients with sepsis were enrolled in this investigation. Ninety-day mortality was significantly higher among G homozygotes than among A allele carriers (P = 0.0032). During intensive care unit stay, G homozygotes experienced higher Sequential Organ Failure Assessment scores (P < 0.001) and a higher demand of vasopressor therapy (P = 0.0107).
Data provide first associative evidence for PD-1 rs11568821 as a prognostic indicator in patients with sepsis.
败血症是一种危及生命的病症。程序性细胞死亡蛋白 1(PD-1)是一种负性共刺激分子,据推测其与发病机制有关,因为高表达与死亡率相关,并且中和抗体在小鼠模型中可改善存活率。PD-1 基因含有一个内含子单核苷酸多态性 rs11568821,它位于转录因子结合位点,据推测会影响 PD-1 的转录。
本研究旨在调查败血症患者的死亡率(90 天)是否与 PD-1 rs11568821 基因型相关。
对来自一所大学医学中心外科重症监护病房的成年败血症白人患者进行为期 90 天的随访,并将死亡率作为主要观察结果。采集血样进行 PD-1 rs11568821 基因分型。在入组时和观察期间,连续器官衰竭评估评分增加,以监测发病率。
本研究共纳入 219 例败血症危重症患者。G 纯合子患者的 90 天死亡率明显高于 A 等位基因携带者(P = 0.0032)。在重症监护病房期间,G 纯合子患者的连续器官衰竭评估评分更高(P < 0.001),需要血管加压素治疗的比例更高(P = 0.0107)。
这些数据首次提供了 PD-1 rs11568821 作为败血症患者预后指标的关联证据。