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Background: Sepsis is a life-threatening condition characterized by organ dysfunction caused by a dysregulated host response to infection. Despite improvements in clinical management, both incidence and mortality remain high. Identifying biomarkers with high sensitivity and specificity is critical for early diagnosis. CD64, an Fcγ receptor upregulated on neutrophils during infection, has emerged as a promising diagnostic indicator. This study aimed to evaluate the diagnostic and mechanistic role of CD64 in pediatric sepsis.
Results: A total of 200 children with sepsis and 166 healthy controls were enrolled. At a cutoff value of 0.165, the CD64 index achieved a diagnostic sensitivity of 87.0% and specificity of 92.8%, outperforming conventional markers such as procalcitonin (PCT), C-reactive protein (CRP), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Mechanistic assays demonstrated that lipopolysaccharide (LPS) stimulation induced CD64 expression through the Protein Kinase B (AKT) signaling pathway. Both LPS exposure and AKT overexpression promoted p65 nuclear translocation, and chromatin immunoprecipitation confirmed p65 binding to the CD64 promoter, thereby enhancing CD64 transcription.
Conclusions: CD64 exhibits superior diagnostic and prognostic performance compared to traditional inflammatory markers and serves as a reliable biomarker for pediatric sepsis. Mechanistically, CD64 upregulation is mediated by the AKT/p65 signaling axis. These findings provide a foundation for integrating CD64 into early diagnostic workflows and developing targeted therapeutic strategies in sepsis management.
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