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Blood, 15 July 2001, Vol. 98, No. 2, pp. 436-441
PHAGOCYTES
Improved superoxide-generating ability by interferon  due to splicing pattern change of transcripts in neutrophils
from patients with a splice site mutation in
CYBB gene
Fuminari Ishibashi,
Tomoyuki Mizukami,
Shiro Kanegasaki,
Lena Motoda,
Ryota Kakinuma,
Fumio Endo, and
Hiroyuki Nunoi
From the Department of Pediatrics, Kumamoto
University School of Medicine; Effector Cell Institute, Research Center
for Advanced Science and Technology, University of Tokyo; Tokushukai
Tokunoshima Hospital, Kagoshima; and Department of Pediatrics, Saitama
Medical Center, Japan.
Chronic granulomatous disease (CGD) is an inherited disorder of
host defense against microbial infections caused by defective activity
of the phagocyte NADPH oxidase. Based on an increase of neutrophil
superoxide-generating ability in response to interferon  (IFN-)
in a single patient with CGD, multicentered group studies demonstrated a beneficial effect of prophylactic IFN-. However, no
apparent increase of the phagocyte superoxide generation was found in
patients enrolled in these studies. The present report offers an
additional kindred in whom an IFN--dependent increase in neutrophil
superoxide production was observed in 3 affected patients. The defect
in the CYBB gene for gp91-phox was identified as an otherwise silent mutation adjacent to the third intron of the
CYBB gene that alters messenger RNA splicing. By molecular analysis, significant differences were found in the splicing pattern of
CYBB gene transcripts in patient neutrophils between 1 and 25 days after administration of IFN-. Furthermore, a complete transcript containing the missing exons could be detected in all specimens after the treatment. The changes in the splicing pattern of
the transcripts and the prolonged effect on superoxide-generating ability of patient neutrophils indicate that IFN- induced a partial correction of the abnormal splicing of CYBB gene
transcripts in myeloid progenitor cells.
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