Impaired LTB4-induced neutrophil chemotactic directionality in myelodysplastic neoplasms patients.

Abstract

Objectives: Myelodysplastic neoplasm (MDS) patients are at a high risk of infections, contributing significantly to morbidity and mortality. While neutrophil dysfunction is considered a primary factor, specific functional defects remain elusive.

Methods: We conducted a comprehensive study involving 90 participants, including controls and de novo MDS patients. We utilized the TAXIScan-FL system to evaluate neutrophil chemotaxis towards leukotriene B4 (LTB4). The global reactive oxygen species (ROS) production by neutrophils were measured by chemiluminescence assay, neutrophil alkaline phosphatase (NAP) was evaluated by enzymatic staining.

Results: MDS patients, irrespective of absolute neutrophil count (ANC) levels, exhibited elevated empirical antimicrobial therapy (EAT) rate compared to controls. Neutrophil migration towards LTB4 was notably impaired, demonstrating reduced velocity and directionality. Interestingly, MDS patients with high ANC still displayed poor directionality and slower migration. MDS patients also had compromised ROS and NAP activity. A noteworthy correlation was observed between EAT rate and chemotactic directionality parameters.

Conclusion: MDS patients face a heightened risk of infection, potentially attributed to impaired neutrophil chemotactic speed and directionality, alongside compromised ROS and NAP activity. Notably, chemotactic directionality emerged as a pivotal factor correlated with antimicrobial therapy. These insights hold significant clinical implications for managing infections in MDS patients, underscoring the importance of targeting specific neutrophil defects for more effective therapeutic strategies.