BACKGROUND: 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. OBJECTIVE: This study aimed at investigating whether mortality (90-day) among patients with sepsis associates with PD-1 rs11568821 genotypes. METHODS: 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. RESULTS: 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). CONCLUSIONS: Data provide first associative evidence for PD-1 rs11568821 as a prognostic indicator in patients with sepsis.
BACKGROUND: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. OBJECTIVE: This study aimed at investigating whether mortality (90-day) among patients with sepsis associates with PD-1rs11568821 genotypes. METHODS: 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-1rs11568821 genotyping. Sequential Organ Failure Assessment scores increased at enrollment and during the observation period to monitor morbidity. RESULTS: 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). CONCLUSIONS: Data provide first associative evidence for PD-1rs11568821 as a prognostic indicator in patients with sepsis.
Authors: Richard S Hotchkiss; Elizabeth Colston; Sachin Yende; Derek C Angus; Lyle L Moldawer; Elliott D Crouser; Greg S Martin; Craig M Coopersmith; Scott Brakenridge; Florian B Mayr; Pauline K Park; June Ye; Ian M Catlett; Ihab G Girgis; Dennis M Grasela Journal: Crit Care Med Date: 2019-05 Impact factor: 7.598
Authors: Ashham Mansur; Benjamin Liese; Maximilian Steinau; Michael Ghadimi; Ingo Bergmann; Mladen Tzvetkov; Aron Frederik Popov; Tim Beissbarth; Martin Bauer; José Hinz Journal: PLoS One Date: 2015-05-28 Impact factor: 3.240
Authors: Ashham Mansur; Yvonne Klee; Aron Frederik Popov; Joachim Erlenwein; Michael Ghadimi; Tim Beissbarth; Martin Bauer; José Hinz Journal: BMJ Open Date: 2015-01-06 Impact factor: 2.692
Authors: Tyler J Loftus; Juan C Mira; Tezcan Ozrazgat-Baslanti; Gabriella L Ghita; Zhongkai Wang; Julie A Stortz; Babette A Brumback; Azra Bihorac; Mark S Segal; Stephen D Anton; Christiaan Leeuwenburgh; Alicia M Mohr; Philip A Efron; Lyle L Moldawer; Frederick A Moore; Scott C Brakenridge Journal: BMJ Open Date: 2017-08-01 Impact factor: 2.692