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.
Highlights
Sepsis is a systemic inflammatory response caused by infection, leading to organ dysfunction and death
Studies have shown that T cells, monocytes and neutrophils in sepsis increase the expression of PD-1 and PD-L1 and that the upregulation of PD-1 or PD-L1 expression is associated with increased mortality [2, 5,6,7,8]
We hope to explore the relationship between the expression of PD-1 on the surface of T lymphocytes and the prognosis of patients diagnosed with sepsis within 24 h of entering the intensive care unit (ICU)
Summary
Sepsis is a systemic inflammatory response caused by infection, leading to organ dysfunction and death. Studies have shown that immunosuppression is the main cause of death in patients with sepsis. Studies have shown that PD-1 expression can be used to predict mortality in patients with sepsis [2, 4]. In an animal experiment with cancer sepsis, compared with the sham operation group, the expression of PD1 on the surface of CD4+ T and CD8+ T cells did not increase on day 1 and day 3 after cecal ligation and puncture (CLP). There are few clinical studies on the relationship between PD-1 expression and prognosis in patients diagnosed with sepsis within 24 h after admission. We hope to explore the relationship between the expression of PD-1 on the surface of T lymphocytes and the prognosis of patients diagnosed with sepsis within 24 h of entering the intensive care unit (ICU)
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