Untargeted Metabolomic Profiling of the Correlation Between Prognosis Differences and PD-1 Expression in Sepsis: A Preliminary Study

Abstract

Objectives: The mortality rate of sepsis remains very high. Metabolomic techniques are playing increasingly important roles in diagnosis and treatment in critical care medicine. The purpose of our research was to use untargeted metabolomics to identify and analyze the common differential metabolites among patients with sepsis with differences in their 7-day prognosis and blood PD-1 expression and analyze their correlations with environmental factors.Methods: Plasma samples from 18 patients with sepsis were analyzed by untargeted LC-MS metabolomics. Based on the 7-day prognoses of the sepsis patients or their levels of PD-1 expression on the surface of CD4+ T cells in the blood, we divided the patients into two groups. We used a combination of multidimensional and monodimensional methods for statistical analysis. At the same time, the Spearman correlation analysis method was used to analyze the correlation between the differential metabolites and inflammatory factors.Results: In the positive and negative ionization modes, 16 and 8 differential metabolites were obtained between the 7-day death and survival groups, respectively; 5 and 8 differential metabolites were obtained between the high PD-1 and low PD-1 groups, respectively. We identified three common differential metabolites from the two groups, namely, PC (P-18:0/14:0), 2-ethyl-2-hydroxybutyric acid and glyceraldehyde. Then, we analyzed the correlations between environmental factors and the common differences in metabolites. Among the identified metabolites, 2-ethyl-2-hydroxybutyric acid was positively correlated with the levels of IL-2 and lactic acid (Lac) (P < 0.01 and P < 0.05, respectively).Conclusions: These three metabolites were identified as common differential metabolites between the 7-day prognosis groups and the PD-1 expression level groups of sepsis patients. They may be involved in regulating the expression of PD-1 on the surface of CD4+ T cells through the action of related environmental factors such as IL-2 or Lac, which in turn affects the 7-day prognosis of sepsis patients.

Expression of PD-1 on Memory T Lymphocytes Predicts 28-Day Mortality of Patients with Sepsis: A Prospective Observational Study

“…Numerous studies have proven that coinhibitory markers such as PD-1 are highly expressed on T cells, and are associated with T-cell apoptosis during sepsis. [23][24][25] That anti-PD-1/PD-L1 has been shown to improve survival in cecal ligation and puncture (CLP) model mice and has entered clinical trials in patients with sepsis. [26][27][28] Our study first reported that it is memory CD4 + T cells and memory CD8 + T cells, rather than naive CD4 + T cells and naive CD8 + T cells, that played critical role in PD-1 mediating signaling in sepsis.…”

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 immunosuppressive molecules, such as PD-1, with increased expression on various types of immune cells, are one of the important mechanisms underlying immunosuppression in sepsis ( 11 , 12 ). It has been reported that the higher the percentage of PD-1 + monocytes, the higher the possibility of nosocomial infection in patients with sepsis ( 7 ). However, PD-1 expression on CD4 + or CD8 + T cells had no effect on nosocomial infection as shown in the study, and this corroborates with finding in a previous report by Wilson et al ( 13 ).…”

“…Programmed death 1 (PD-1), an immunoreceptor tyrosine-based inhibitory motif–containing receptor or an inhibitory member of the CD28 family, expressed on activated T cells, B cells, and monocytes and likely regulates these cell types ( 6 ), may be related to nosocomial infection in patients with sepsis. Among septic shock patients, elevated PD-1 combined with PD–ligand 1 of CD4 + T cell resulted in increased nosocomial infections and mortality ( 7 ). This may be attributed to PD-1 interacted with PD-1 combined with PD–ligand 1 of antigen-presenting cells (APCs) that inhibited CD4 + or CD8 + T cells and reduced interleukin 2 (IL-2) production ( 8 ).…”

Proteomic Approaches to Unravel Mechanisms of Antibiotic Resistance and Immune Evasion of Bacterial Pathogens

“…Mass spectrometry and “omics” strategies allow for untargeted profiling of thousands of proteins and metabolites from human biological samples obtained from septic patients. Differential expression of, or modifications to, these proteins and metabolites provides a more reliable source of diagnostic biomarkers for sepsis ( 135 , 137 ).…”