Clinical Utility of Neutrophil CD64 Expression in Diagnosing Sepsis and Immune Dysregulation: Insights from Flow Cytometry

Neutrophil CD64 expression, assessed via flow cytometry, has emerged as a critical biomarker for distinguishing bacterial infections from non-infectious inflammatory conditions. CD64, a high-affinity Fcγ receptor, plays a pivotal role in the immune response by facilitating neutrophil activation, phagocytosis, and cytokine release. In normal physiological states, neutrophils exhibit low CD64 expression, which significantly increases during bacterial infections and systemic inflammatory responses such as sepsis. Studies indicate that CD64 expression correlates with disease severity, making it a valuable tool in clinical decision-making. Additionally, advancements in highdimensional and spectral flow cytometry have enhanced the accuracy of immune cell characterization, enabling a deeper understanding of neutrophil function in various pathological states. Despite its diagnostic potential, challenges remain regarding standardization of assay protocols, cut-off values, and interpretation across different patient populations. This review discusses the latest developments in flow cytometry techniques, computational tools for data analysis, and the integration of CD64 measurement into routine clinical practice. We also explore emerging trends, such as single-cell cytometry and mass cytometry (CyTOF), which offer new insights into neutrophil heterogeneity and immune regulation. Neutrophil CD64 expression serves as a reliable biomarker for bacterial infections and inflammatory conditions. While flow cytometry remains the gold standard for CD64 analysis, ongoing research aims to refine methodologies for broader clinical application. Future studies should focus on optimizing assay protocols, establishing reference ranges, and integrating CD64 assessment into multi-parameter diagnostic panels to improve patient outcomes.