Abstract

Idiopathic neutropenia (IN) is a disorder that can lead to severe, life-threatening infections. IN in children is usually characterized by decreased neutrophil counts ( < 1500/ μl) and can result in reduced monocyte count and phagocyte function. Since no current therapies exist and the pathophyisiology is not fully understood, we sought to investigate immune mechanisms of IN in children. We investigated the role of circulating Fas Ligand in mediating IN by comparing IN patients to healthy control (HC) patients. Our results suggest that high levels of FasL contribute to IN pathology. Additionally, the plasma from acute IN patients was found to have higher levels of soluble FasL than chronic IN patients. When incubating HC neutrophils with IN patient plasma, higher levels of apoptosis were seen. The plasma-derived factor in inducing apoptosis was found to be preferentially specific for neutrophils. Addition of anti-sFasL antibodies to IN patient plasma resulted in a significant decrease in neutrophil apoptosis. In summary, these data suggest that sFasL in IN patient plasma may reduce neutrophil cell death and that the Fas/FasL apoptotic pathway may play a role in the pathology of idiopathic neutropenia.

Keywords: Neutropenia, pediatric hematology, apoptosis, mechanism, neutrophil, Fetal alcohol syndrome (FAS), Plasma, necrosis, monocyte, phagocyte