The use of rh-G-CSF in chronic autoimmune neutropenia: Reversal of autoimmune phenomena, a case history

An 8-year-old boy had been suffering from chronic autoimmune neutropenia for more than 5 years. The neutropenia proved to be resistant to high-dose steroids and intravenous (either low- or high-dose) immunoglobulin (Ig) therapy. The chronic autoimmune thrombocytopenia and recurrent phases of autoimmune haemolytic anaemia did. however, respond to high-dose prednisone. Other signs of immune dysregulation in this patient consisted of insulin-dependent diabetes mellitus type I (IDDM) and an acquired hypogammaglobulinaemia, most compatible with common variable immunodeficiency (CVI). Prior to rhG-CSF therapy the child had suffered for more than 2 years from recurrent life-threatening bacterial infections. Anti-neutrophil autoantibodies had pan-Fc gamma RIII (CD16, NA1/NA2) specificity. The neutropenia as well as the antineutrophil autoantibodies disappeared when subcutaneous rhG-CSF therapy was started. Upon tapering rhG-CSF, anti-Fc gamma RIII antibodies reappeared together with an absolute neutropenia. Renewed administration resulted again in the normalization of symptoms. Soluble Fc gamma RIII (sFc gamma RIII) antigen levels in plasma increased dramatically during rhG-CSF treatment. These high levels of sFc gamma RIII together with increased numbers as well as decreased apoptotic reactions of neutrophils apparently result in adsorption of the autoantibodies in vivo, contributing to the normalization of autoimmune-mediated neutropenia upon rhG-CSF treatment. Long-term administration of rhG-CSF represents an alternative in the treatment of autoimmune neutropenia.