Predictive Value of Soluble Programmed Cell Death Ligand-1 in the Progression of Septic Patients to Chronic Critical Illness in the Intensive Care Unit: A Prospective Observational Clinical Study

Abstract

Background: As an immune marker, serum soluble programmed cell death ligand-1 (sPD-L1) is significantly increased in sepsis and is predictive of mortality. We investigated the prognostic value of sPD-L1 in postseptic immunosuppression and progression to chronic critical illness (CCI). Methods: Adults with sepsis in intensive care units (ICUs) for the first time were screened and assigned to either a CCI group (ICU stay ≥14 days with persistent organ dysfunction) or a rapid recovery (RAP) group based on clinical outcome. Data regarding basic admission information and clinical parameters were collected and compared across the two groups. Serum sPD-L1 levels were detected by enzyme-linked immunosorbent assay at admission and on the seventh day (D7). Logistic regression analysis was used to determine the factors affecting septic patients' lymphocytopenia diagnosis on day 7 and CCI progression during hospitalization. The receiver operating characteristic curve and DeLong test were used to assess variable predictive power. Results: During the study period, a total of 166 septic patients were admitted to the ICU, and 91 septic patients were enrolled after screening. Compared with those in healthy individuals, the sPD-L1 levels in septic patients were significantly higher and positively correlated with traditional inflammatory markers and disease severity scores (P < 0.05). In a multivariate regression analysis, sPD-L1 alone predicted lymphocytopenia on day 7 (P < 0.05). In the sepsis cohort, 59 patients (64.8%) experienced RAP, and 32 patients (35.2%) developed CCI. Compared with the RAP group, the patients in the CCI group had a higher mean age, greater severity of disease, and higher mortality (P < 0.05). D7-sPD-L1 remained higher in the CCI group, and the area under the curve that predicted the occurrence of CCI was equivalent to the APACHE II score, with areas under the curve of 0.782 and 0.708, respectively. Conclusions: The severity of infection and immunosuppression in sepsis may be linked to serum sPD-L1. D7-sPD-L1 is valuable in predicting the progression of CCI in patients.

Adverse outcomes and an immunosuppressed endotype in septic patients with reduced IFN-γ ELISpot

“…ELISpot has emerged as a powerful method to assess immunological status in a variety of clinical disorders (25)(26)(27)(28), including septic and critically ill patients (20,21,29,30). It offers several theoretical advantages over other current metrics -for example, cell phenotypes such as ALC (31)(32)(33)(34) and HLA-DR expression on CD14 + blood cells (35,36); plasma protein concentrations such as procalcitonin (37)(38)(39)(40), IL-6 (41)(42)(43), and sPD-L1 (44,45); or blood transcriptomics (24,46,47) -used to predict both the severity of the host response and the immunosuppressed endotype. ELISpot, unlike these static measures, assesses one component of the functional status of the host protective immune response.…”

Peripheral PD-1+NK cells could predict the 28-day mortality in sepsis patients

“…Observational studies have noted that levels of soluble programmed cell death ligand-1 (sPD-L1) in the peripheral blood are elevated in septic patients and positively correlated with CRP and PCT levels. However, these levels are not associated with poor prognosis at an early stage ( 45 ). Similarly, some immunosuppressive biomarkers like monocytic HLA-DR expression proved inadequate for predicting sepsis mortality in the initial phase.…”

Adverse Long-Term Outcomes and an Immune Suppressed Endotype in Sepsis Patients with Reduced Interferon-γ ELISpot: A Multicenter, Prospective Observational Study

“…ELISpot has emerged as a powerful method to assess immunological status in a variety of clinical disorders (27-30), including sepsis and critically ill patients (20,21,31,32). It offers several theoretical advantages over other current metrics – for example, cell phenotypes (such as ALC (33-36) and HLA-DR expression on CD14 + blood cells (37,38)), plasma protein concentrations (such as procalcitonin (39-42), IL-6 (43-45) and sPD-L1 (46,47)) or blood transcriptomics (26,48,49) – used to predict both the severity of the host response and the immunosuppressed endotype. ELISpot, unlike these static measures, assesses one component of the functional status of the host protective immune response.…”