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

Abstract Background The 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. Methods A 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. Results A 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). Conclusion PD-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.