Histone Lactylation in Immune Cells and Its Predictive Role in Sepsis Progression: A Prospective Observational Study.

BACKGROUND

Sepsis, a life-threatening condition caused by infection, induces dysregulated immune responses. Lactylation is a lactate-derived posttranslational modification with roles in various cellular processes. We investigated lactylation levels in the immune cells of patients with sepsis and evaluated their association with disease progression.

METHODS

In this prospective cohort study, blood samples were collected on days 1 and 3 from 58 intensive care unit patients, including critically ill controls and sepsis patients (survivors and nonsurvivors). Biochemical and clinical data were analyzed, and immune cells were isolated to measure pan-lysine lactylation (Pan Kla), H4K5la, and H3K56la levels using flow cytometry.

RESULTS

Patients with sepsis exhibited significantly elevated neutrophil H4K5la levels compared with critically ill controls on day 1 (231.6 [174.9-361.9] vs. 127.5 [69.4-168.9] mean fluorescence intensity [MFI], P  < 0.0001); similar trends were observed in monocytes, B cells, and T cells. Multivariate analysis identified neutrophil H4K5la levels as an independent predictor of sepsis. The combination of day 1 neutrophil H4K5la and C-reactive protein levels improved diagnostic performance (area under the receiver operating characteristic curve = 0.902 [95% confidence interval, 0.795-0.964]). On day 3, nonsurvivors showed lower lactylation levels than survivors (monocyte Pan Kla: 79.8 [54.9-106.1] vs. 133.2 [112.3-259.2] MFI, P  = 0.0334; T-cell H3K56la: 15.5 [8.2-28.1] vs. 37.2 [23.9-71.4] MFI, P  = 0.0143).

CONCLUSIONS

Immune cell lactylation may serve as a biomarker for sepsis progression. The combination of neutrophil H4K5la and C-reactive protein enhances early diagnostic accuracy; reduced lactylation on day 3 may indicate poor prognosis.