Two X-linked chronic granulomatous disease patients with unusual NADPH oxidase properties
B Wolach, A Broides, T Zeeli, R Gavrieli… - Journal of clinical …, 2011 - Springer
B Wolach, A Broides, T Zeeli, R Gavrieli, M De Boer, K Van Leeuwen, J Levy, D Roos
Journal of clinical immunology, 2011•SpringerBackground Chronic granulomatous disease (CGD) is an immune deficiency syndrome
caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase,
the enzyme that generates reactive oxygen species (ROS) in phagocytizing leukocytes. This
study evaluates the NADPH oxidase capacity in two X-linked CGD patients with mutations in
gp91 phox that alter the regions in this membrane-bound NADPH oxidase component
involved in docking of the cytosolic component p47 phox. Materials and Methods Hydrogen …
caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase,
the enzyme that generates reactive oxygen species (ROS) in phagocytizing leukocytes. This
study evaluates the NADPH oxidase capacity in two X-linked CGD patients with mutations in
gp91 phox that alter the regions in this membrane-bound NADPH oxidase component
involved in docking of the cytosolic component p47 phox. Materials and Methods Hydrogen …
Background
Chronic granulomatous disease (CGD) is an immune deficiency syndrome caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the enzyme that generates reactive oxygen species (ROS) in phagocytizing leukocytes. This study evaluates the NADPH oxidase capacity in two X-linked CGD patients with mutations in gp91phox that alter the regions in this membrane-bound NADPH oxidase component involved in docking of the cytosolic component p47phox.
Materials and Methods
Hydrogen peroxide and superoxide generation, bactericidal activity, and NADPH oxidase protein expression by the patients’ neutrophils were measured, and genetic analysis was performed.
Results
We report two patients, each with a novel missense mutation in CYBB, the gene that encodes gp91phox. Surprisingly, neutrophils from these patients showed total absence of superoxide production, although they retained 13–30% of the hydrogen peroxide production capability. We speculate that this is due to direct electron transfer from flavin adenine dinucleotide (FAD) in gp91phox to oxygen, leading to inefficient hydrogen peroxide formation instead of efficient superoxide production.
Conclusions
X-linked CGD patients with mutations that alter the gp91phox protein in regions involved in docking of the cytosolic NADPH oxidase component p47phox may have higher than expected hydrogen peroxide generation capability.
Springer