Idiopathic neutropenia of childhood is associated with Fas/FasL expression

Idiopathic neutropenia (IN) in children is characterized by decreased neutrophil counts (<1500/mu l), can be acute or chronic (greater than 6 months duration). The pathophysiology is not well understood; therefore, potential mechanisms of pediatric IN were investigated. An increase in Fas transcripts in neutrophits of IN patients compared to age-matched healthy control (HC) neutrophits was observed (p<0.005). Increased expression of Fas protein was found in IN neutrophits, white Fas surface expression on other immune cells was similar. Plasma from acute IN patients had higher protein levels of soluble FasL than chronic IN patients. When HC neutrophits were incubated in plasma from IN patients, greater rates of apoptosis were observed. Biochemical studies suggest the apoptotic factor(s) in plasma is heat-sensitive, non-IgG, and 12-50 kD protein. Addition of anti-sFasL blocking antibodies to patient plasma caused a statistically significant decrease in neutrophil. apoptosis. These studies show that the Fas/FasL pathway could be associated with neutrophil. apoptosis in childhood IN. (C) 2008 Elsevier Inc. All rights reserved.