ELEVATED PD-1/CD28 RATIO RATHER THAN PD-1 EXPRESSION IN CD8(+) T CELLS PREDICTS NOSOCOMIAL INFECTION IN SEPSIS PATIENTS: A PROSPECTIVE, OBSERVATIONAL COHORT STUDY

The expression of programmed cell death 1 receptor (PD-1) and CD28 on CD8(+) T cells is considered to be related to immune function and prognosis markers in patients with sepsis. However, the relationship between the ratio of PD-1/CD28 and nosocomial infection has not been elucidated. Methods: A prospective, observational cohort study was conducted in a general intensive care unit. Patients were enrolled according to the sepsis-3 criteria and peripheral blood samples were collected within 24 hours of enrollment. Programmed cell death 1 receptor and CD28 expression on CD8(+) T cells was assayed on day 1. Patients were followed up until 28 days. Multivariate regression analysis was used to assess independent risk factors for nosocomial infection. The accuracy of biomarkers for nosocomial infection and mortality was determined by the area under the receiver operating characteristic curve analysis. The association between biomarkers and 28-day mortality was assessed by Cox regression survival analysis. Results: A total of 181 patients were recruited, and 68 patients were finally included for analysis. Of these, 19 patients (27.9%) died during 28 days and 22 patients (32.4%) acquired nosocomial infection. The PD-1/CD28 ratio of patients with nosocomial infection was significantly higher than those without (0.27 [0.10–0.55] vs. 0.15 [0.08–0.28], P = 0.025). The PD-1/CD28 ratio in CD8(+) T cells (odds ratio, 53.33; 95% confidence interval, 2.39–1188.22, P = 0.012) and duration of mechanical ventilation (odds ratio, 1.14; 95% confidence interval, 1.06–1.24; P = 0.001) were independently associated with nosocomial infection. The area under the receiver operating characteristic curve of PD-1/CD28 ratio in CD8(+) T cells was 0.67 (0.52–0.82). The PD-1/CD28 ratio in CD8(+) T cells of the nonsurvivors was significantly higher than the survivors (0.23 [0.15–0.52] vs. 0.14 [0.07–0.32]); Cox regression analysis showed that the survival time of patients with PD-1/CD28 ratio in CD8(+) T cells of 0.13 or greater was shorter compared with patients with lower levels (hazard ratio, 4.42 [1.29–15.20], χ(2) = 6.675; P = 0.010). Conclusions: PD-1/CD28 ratio in CD8(+) T cells at admission may serve as a novel prognostic biomarker for predicting nosocomial infection and mortality.