Rheumatology Advance Access originally published online on October 25, 2005
Rheumatology 2006 45(2):178-181; doi:10.1093/rheumatology/kei135
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Abnormal apoptosis in chronic granulomatous disease and autoantibody production characteristic of lupus
Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Correspondence to: K. E. Sullivan, Immunology, CHOP, 34th St and Civic Ctr Blvd, Philadelphia, PA 19104, USA. E-mail: sullivak{at}mail.med.upenn.edu
Objectives. 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.
KEY WORDS: Lupus, Chronic granulomatous disease, Glomerulonephritis autoantibodies