Severe congenital neutropenia (SCN) or Kostmann syndrome is a disorder of 
myelopoiesis characterized by a maturation arrest at the stage of promyelocytes 
or myelocytes in bone marrow and absolute neutrophil counts less than 200/microL 
in peripheral blood. Treatment of these patients with granulocyte 
colony-stimulating factor (G-CSF) leads to a significant increase in circulating 
neutrophils and a reduction in infection-related events in more than 95% of the 
patients. To date, little is known regarding the underlying pathomechanism of 
SCN. G-CSF-induced neutrophils of patients with SCN are functionally defective 
(eg, chemotaxis, superoxide anion generation, Ca(++ )mobilization). Two 
guanosine triphosphatases (GTPases), Rac2 and RhoA, were described to be 
involved in many neutrophil functions. The expression of these GTPases and their 
regulation in patients' neutrophils were of interest. This study determined that 
the guanosine diphosphate (GDP)-dissociation inhibitor RhoGDI is overexpressed 
at the protein level in patients' neutrophils and that overexpression is a 
result of G-CSF treatment. RhoA and LyGDI are expressed at similar levels, 
whereas Rac2 shows a decreased expression. In addition, association of Rac2 and 
RhoGDI or LyGDI is abrogated or not detectable based on the low Rac2 expression 
in patients' neutrophils. (Blood. 2000;95:2947-2953)