| ObjectiveTrauma is the main cause of death and disability in young adults in daily work and life.The important reason for the high mortality of trauma is the disturbance of body immune function after injury,which can be manifested clinically as systemic inflammatory response syndrome(SIRS),Sepsis,and multiple organ dysfunction syndrome(MODS).Programmed cell death-1(PD-1)and programmed death ligand-1(PD-L1)are negative costimulatory molecules of immune cells,which play an important role in regulating the proliferation,differentiation and activity of immune cells.The purpose of this study was to summarize the dynamic changes of PD-1 on T lymphocytes and PD-L1 on monocyte expression in peripheral blood at the early stage of trauma patients,and to analyze the correlation between these changes and the concentration of inflammatory mediators,the severity of trauma and the prognosis within 28 days.MethodsA prospective case-control study was conducted in 60 trauma patients with different severity of trauma(according to the AIS-ISS score at admission,patients with different severity of trauma were divided into three groups: mild/moderate trauma group,severe trauma group and very severe trauma group)and 20 healthy volunteers(control group).The whole blood 2ml and serum 1ml were collected on day0,day 1,day 3,day 5 and day 7 after trauma,and the levels of PD-1% on T lymphocytes and,PD-L1% on monocytes of peripheral blood were measured by flow cytometry.Serum TNF-α,IL-6 and IL-10 levels were measured by ELISA kit,and calculate the TNF-α/IL-10 ratio.Detection of c-reactive protein(CRP)by immunochemiluminescence assay and detection of procalcitonin(PCT)concentration by immunofluorescence chromatography.The expression of CD4+/CD8+ T lymphocyte PD-1 and CD14+ monocyte PD-L1 in trauma patients were analyzed and compared,at the same time,we observed the difference of the expression of PD-1/PD-L1 between different subgroups of trauma patients complicated with shock,sepsis and death within 28 days.Pearson correlation analysis was used to investigate the relationship between the dynamic expression of PD-1 T lymphocytes and PD-L1 on monocytes of peripheral blood and AIS-ISS scores,APACHE II scores,SOFA scores and Inflammatory cytokines level in the early stage of trauma.Logsitic regression model and Cox proportional hazard regression model were used to analyze the independent risk factors of sepsis and death in trauma patients within 28 days.The cutoff point was determined by the receiver operating characteristic curve(ROC)and the survival curve of kaplan-meier was drawn.ResultsIn mild / moderate trauma group(MT,AIS-ISS<16),severe trauma group(ST,16≤AIS-ISS < 25),very severe trauma group(VST,AIS-ISS≥25),the peripheral CD4+/CD8+T lymphocytes PD-1% and CD14+ monocytes PD-L1% expression were increased than the level of healthy volunteers(p<0.05).The more severe the trauma,the higher expression level of CD4+/CD8+T lymphocytes PD-1%,CD14+ monocytes PD-L1% and inflammatory factors(serum TNF-α,IL-6 and IL-10),and the lower TNF-α/IL-10 ratio.The expression level of CD4+/CD8+T lymphocytes PD-1% and CD14+ monocytes PD-L1% were higher in shock group,sepsis group and death group.AIS-ISS scores,APACHE II scores and SOFA scores were positively correlated with the expression of CD4+/CD8+T lymphocytes PD-1% and CD14+ monocytes PD-L1%(p<0.05).The concentrations of PCT,CRP,TNF-α,IL-6,IL-10 were positively correlated with the expression of PD-1/PD-L1 at some time points,and the ratio of TNF-α/IL-10 was negatively correlated with the expression of PD-1/PD-L1 within 72 hours after trauma(p<0.05).The result of Cox proportional hazard regression model analysis was that CD14+ monocytes PD-L1% Day1 and the severity of trauma were risk factors for death of trauma patients within 28 days(p<0.05).The ROC results showed that the area under curve(AUC)within 28 days mortality of CD14+ monocytes PD-L1% Day1 was 0.927(p<0.05),and the cutoff point of CD14+monocytes PD-L1% Day1 was 32.60%.According to the CD14+ monocytes PD-L1%Day1 cut-off point,the 28-day survival curve of trauma patients was drawn.The logarithmic rank log-rank test showed that there was a significant difference between CD14+ monocytes PD-L1% Day1<32.60% and≥32.60% in the survival time of the trauma patients(χ2=35.434,p<0.05).In addition,Logsitic regression analysis showed that SOFA score was an independent risk factor for sepsis in trauma patients within 28days(p<0.05).CD4+/CD8+T lymphocytes PD-1% and CD14+ monocytes PD-L1%was not a prediction factor of sepsis within 28 days.ConclusionIn conclusion,the overexpression of PD-1 on T lymphocytes and PD-L1 on monocytes of peripheral blood can be detected at the early stage of trauma and it may be associated with the severity of trauma,shock and sepsis,AIS-ISS scores,APACHE II scores and SOFA scores as well as the concentration of inflammatory mediators.The increase of monocyte PD-L1 on the first day after injury was an independent risk factor for death within 28 days,but the PD-1/PD-L1 of T lymphocytes and monocytes was not a prediction factor of sepsis within 28 days. |
