title: Severe congenital neutropenia: clinical effects and neutrophil function during treatment with granulocyte colony-stimulating factor.
abstract: We studied neutrophil function and clinical responses in seven patients with severe congenital neutropenia (SCN) after they received treatment with recombinant human granulocyte colony stimulating factor (rhG-CSF). Two subpopulations of patients with SCN were defined by their pattern of absolute neutrophil response, superoxide production, and cytochrome b559 levels. One group had an oscillating absolute neutrophil count and reduced ability to produce superoxide and cytochrome b559 (n = 4), and the second group had a relatively constant absolute neutrophil count response with normal superoxide and cytochrome levels (n = 3). Neutrophils from both groups had decreased surface expression of FcRIII and abnormal upregulation of the C3bi receptor (CR3). All patient neutrophils, however, had normal contents of the primary granule constituent, beta-glucuronidase, and the specific granule constituent, vitamin B 12 binding protein. The clinical response to rhG-CSF was evident by marked improvement in the degree of periodontitis and reduction in the number of oral ulcers in both groups of patients. Although neutrophil function is not completely normal in patients with SCN, it is likely that enough redundancy exists in neutrophil bactericidal capacity to promote normal host response to inflammation.
authors.affiliation: Department of Pediatrics and Internal Medicine, University of Michigan, Ann Arbor.
authors.forename: B
authors.initials: B
authors.lastname: Weston
authors.forename: R F
authors.initials: RF
authors.lastname: Todd
authors.forename: R
authors.initials: R
authors.lastname: Axtell
authors.forename: K
authors.initials: K
authors.lastname: Balazovich
authors.forename: J
authors.initials: J
authors.lastname: Stewart
authors.forename: B J
authors.initials: BJ
authors.lastname: Locey
authors.forename: L
authors.initials: L
authors.lastname: Mayo-Bond
authors.forename: P
authors.initials: P
authors.lastname: Loos
authors.forename: R
authors.initials: R
authors.lastname: Hutchinson
authors.forename: L A
authors.initials: LA
authors.lastname: Boxer
mesh_terms: D018821:CD18 Antigens; D005891:Gingivitis / Q000209:etiology; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D016177:Macrophage-1 Antigen / Q000032:analysis; D009503:Neutropenia / Q000097:blood / Q000151:congenital* / Q000628:therapy; D009504:Neutrophils / Q000187:drug effects*; D011961:Receptors, Fc / Q000032:analysis; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D016028:Receptors, Leukocyte-Adhesion; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor