Abstract
BACKGROUND: Sepsis is characterized by a dysregulated immune response to infection, with a balance between hyperinflammation and immunosuppression, which determines the patient's immune status. Real-time monitoring of the immune status in sepsis is crucial for guiding immunotherapy. However, reliable biomarkers are lacking. This study aims to identify a panel of biomarkers for rapid bedside assessment of immune status in sepsis to guide immunotherapy decisions. RESULTS: TBX21, GNLY, PRF1, and IL2RB represent the immune status in sepsis. These genes demonstrated discriminatory power in the external validation, with area under the curve values ranging from 0.891 to 0.909 across several machine learning models. 99 double-blind randomized patients with sepsis were clustered into two endotypes on the basis of the expression of the four-gene panel. Higher 90-day mortality was observed in patients with sepsis treated with hydrocortisone (Odds ratio 12.46, 95% confidence intervals 3.11 to 65.72) or thymosin (Odds ratio 4.17, 95% confidence intervals 1.13 to 16.51) within the high-expression 4-gene panel endotype, but not in another endotype. CONCLUSIONS: The results support the potential utility of a four-gene panel to assess immune status and guide immunotherapy; further prospective validation and translational studies are warranted. Trial registration National Medical Research Registration and Filing Information of China, 2022ZDSYLL196-P01. Registered 26 May 2023, https://www.medicalresearch.org.cn/login.