title: Apoptotic neutrophils in the circulation of patients with glycogen storage disease type 1b (GSD1b).
abstract: Glycogen storage disease type 1b (GSD1b) is a rare autosomal recessive disorder characterized by hypoglycemia, hepatomegaly, and growth retardation, and associated-for unknown reasons- with neutropenia and neutrophil dysfunction. In 5 GSD1b patients in whom nicotin-amide adenine dinucleotide phosphate-oxidase activity and chemotaxis were defective, we found that the majority of circulating granulocytes bound Annexin-V. The neutrophils showed signs of apoptosis with increased caspase activity, condensed nuclei, and perinuclear clustering of mitochondria to which the proapoptotic Bcl-2 member Bax had translocated already. Granulocyte colony-stimulating factor (G-CSF) addition to in vitro cultures did not rescue the GSD1b neutrophils from apoptosis as occurs with G-CSF-treated control neutrophils. Moreover, the 2 GSD1b patients on G-CSF treatment did not show significantly lower levels of apoptotic neutrophils in the bloodstream. Current understanding of neutrophil apoptosis and the accompanying functional demise suggests that GSD1b granulocytes are dysfunctional because they are apoptotic.
authors.affiliation: Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, the Netherlands. t.w.kuijpers@amc.uva.nl
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Maianski
authors.forename: Anton T J
authors.initials: AT
authors.lastname: Tool
authors.forename: G Peter A
authors.initials: GP
authors.lastname: Smit
authors.forename: Jan Peter
authors.initials: JP
authors.lastname: Rake
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
authors.forename: Gepke
authors.initials: G
authors.lastname: Visser
mesh_terms: D000293:Adolescent; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D020169:Caspases / Q000097:blood; D002467:Cell Nucleus / Q000473:pathology; D002634:Chemotaxis, Leukocyte; D002648:Child; D002675:Child, Preschool; D005260:Female; D005953:Glycogen Storage Disease Type I / Q000097:blood*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007223:Infant; D008297:Male; D008928:Mitochondria / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D009503:Neutropenia; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology; D010587:Phagocytosis; D011518:Proto-Oncogene Proteins / Q000097:blood; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
chemical_list: D017304:Annexin A5; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016179:Granulocyte Colony-Stimulating Factor; D019255:NADPH Oxidases; D020169:Caspases