Relationship Between the Expression of PD-1 and CTLA-4 on T Lymphocytes and the Severity and Prognosis of Sepsis

Abstract

Purpose

The study aimed to investigate the relationship between the expression of PD-1 and CTLA-4 on the surface of peripheral blood T lymphocyte subsets in patients with sepsis and the severity and prognosis of the disease.

Patients and Methods

The study included patients with sepsis who were admitted to the intensive care unit. The expression of PD-1 and CTLA-4 on T lymphocyte subsets was detected by flow cytometry, and the severity of sepsis was assessed using the SOFA score.

Results

The expression of PD-1 on CD4⁺T cells, PD-1 on Tregs, and CTLA-4 on Tregs increased with the severity of the disease (P<0.05). Multivariate logistic regression analysis showed that PD-1 expression on CD4⁺T cells, CTLA-4 expression on Tregs, and the SOFA score were independent risk factors for 28-day mortality in patients with sepsis (P<0.05). The area under the curve of the SOFA score combined with the expression of PD-1 on CD4⁺T cells and CTLA-4 on Treg cells was significantly higher than any single indicator (P<0.05). Patients with high expression of PD-1 on CD4⁺T cells (>31.25%) and CTLA-4 on Tregs (>12.64%) had a lower 28-day survival rate (P<0.05).

Conclusion

The increased expression of PD-1 and CTLA-4 on CD4⁺T cells and Tregs is significantly associated with the severity and prognosis of sepsis patients. The combination of the SOFA score and the expression of PD-1 on CD4⁺T cells and CTLA-4 on Tregs can further improve the prognostic predictive value. These findings may be promising biomarkers for prognostic assessment, risk stratification, and identification of immunosuppression in patients with sepsis.

Keywords:

• sepsis
• T lymphocyte subsets
• programmed cell death receptor-1
• cytotoxic T lymphocyte antigen-4
• prognosis

Data Sharing Statement

The datasets used to support the findings of this study are available from the first author and corresponding authors on reasonable request.

Ethics Approval and Consent to Participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University. Written informed consent was obtained from the patients or, if not possible, from their relative as designed by ethic committee.

Acknowledgments

The authors thank the subjects for their participation in this study and the staff of the hospital for their help in collecting and recording the data.

Disclosure

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Additional information

Funding

This work was supported by the Natural Science Project of Guizhou Province (Grant No. ZK-2022-441) and Doctoral Research Startup Fund in 2021 (Grant No. gyfybsky-2021-47).