PD-1 in Tregs predicts the survival in sepsis patients using sepsis-3 criteria: A prospective, two-stage study

Abstract

BackgroundThe expression of Tregs co-signaling molecules serves as the marker of immune dysfunction. The present study aimed to verify their predictive role in the 28-day mortality of sepsis patients. MethodsA prospective, observational, two-stage cohort study was conducted. The patients who fulfilled the sepsis-3 criteria were enrolled, and peripheral blood samples were collected within 24 h post-enrollment. The expression of the four co-signaling molecules of Tregs, namely, PD-1, CD28, PD-L1 and CD86, was measured, and sequential organ failure assessment (SOFA) scores were recorded on day 1 of inclusion. Patients were followed up for 28 days or, otherwise, deceased. Multivariate regression analysis was used to assess the independent risk factors for 28-day mortality, and a prognostic prediction model was established, which was verified in the validation set. ResultsA total of 292 patients were recruited in the study, of which 120 patients were finally included in the analysis, that is 58 patients in stage I (test set) and 62 patients in stage II (validation set). In stage I, 14 (24.1%), patients died during 28 days, and the expression of PD-1 in Tregs (OR:1.037;95%CI:1.003–1.071) and SOFA scores(OR:1.262;95%CI:1.046–1.524) were independent risk factors for 28-day mortality. The ability of Tregs PD-1 in predicting 28-day mortality was validated in stage II (AUC = 0.792). ConclusionPD-1 overexpression in Tregs was associated with poor outcomes, and PD-1 in Tregs is considered to be a valuable tool for the prediction of prognosis in septic patients using sepsis-3.0 criteria.