title: Abnormal apoptosis in chronic granulomatous disease and autoantibody production characteristic of lupus.
abstract: OBJECTIVE
  Patients with chronic granulomatous disease and carrier mothers of patients with chronic granulomatous disease are predisposed to developing various forms of lupus. This disorder is a neutrophil defect in intracellular killing. Abnormal apoptosis has been described. We hypothesized that abnormal apoptosis occurring in neutrophils of patients made them more immunogenic.
  
  
  METHODS
  Human patients with chronic granulomatous disease were examined for abnormalities of neutrophil apoptosis by flow cytometry. To model the effect of abnormal apoptosis, a murine model was used. Apoptotic cells from either wild type or mice with chronic granulomatous disease were injected into either wild type or chronic granulomatous disease mice and autoantibodies were determined by ELISA.
  
  
  RESULTS
  Our studies found that human and murine neutrophils carrying the gp91 form of chronic granulomatous disease had impaired exposure of phosphatidyl serine on the surface. Other markers of apoptosis were largely normal. Injection of apoptotic neutrophils from gp91 knockout mice into gp91 knockout mice led to the development of characteristic autoantibodies of lupus.
  
  
  CONCLUSIONS
  Humans with chronic granulomatous disease may be at an increased risk of developing lupus due to abnormal apoptosis and abnormal clearance of apoptotic cells.
authors.affiliation: Immunology, CHOP, 34th St and Civic Ctr Blvd, Philadelphia, PA 19104, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Sanford
authors.forename: A R
authors.initials: AR
authors.lastname: Suriano
authors.forename: D
authors.initials: D
authors.lastname: Herche
authors.forename: K
authors.initials: K
authors.lastname: Dietzmann
authors.forename: K E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006105:Granulomatous Disease, Chronic / Q000150:complications* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D011971:Receptors, Immunologic / Q000235:genetics
chemical_list: D001323:Autoantibodies; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic