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

Int Immunopharmacol. 2020 Dec;89(Pt A):107175. doi: 10.1016/j.intimp.2020.107175. Epub 2020 Nov 19.

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.

Keywords: Organ dysfunction scores; Prognosis; Programmed cell death 1 receptor (PD-1); Sepsis; T-lymphocytes, regulatory.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism*
  • Prospective Studies
  • ROC Curve
  • Sepsis / mortality*
  • Sepsis / pathology*
  • Survival
  • T-Lymphocytes, Regulatory

Substances

  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor