X-linked chronic granulomatous disease (XL-CGD), a rare primary immunodeficiency due to a defect in the gp91<sup>phox</sup> NADPH oxidase subunit, results in recurrent, severe infection, inflammation, and autoimmunity.
Germline mutations in CYBB, the human gene encoding the gp91(phox) subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD).
We further demonstrate that additive gene transfer using lentiviral vectors encoding gp91(phox) is capable of restoring NADPH-oxidase activity in mature neutrophils derived from X-CGD iPSC.
Long-term high-level reconstitution of NADPH oxidase activity in murine X-linked chronic granulomatous disease using a bicistronic vector expressing gp91phox and a Delta LNGFR cell surface marker.
Early data from experiments in which low-dose radiation-conditioned X-CGD recipients were transplanted with retrovirus-transduced X-CGD marrow cells show that gene-corrected neutrophils can be detected by NBT assay for NADPH oxidase activity reconstitution 4 months posttransplant, although these levels are much lower than the 50%-70% gene-corrected cell detected in lethally irradiated recipients.
CGD is caused by mutations in any of 4 genes encoding components of nicotinamide adenine dinucleotide phosphate (reduced form; NADPH) oxidase, the multisubunit enzyme that produces the precursor of these oxidants, superoxide.
CGD is caused by defects in the phagocyte NADPH oxidase, a multiprotein enzyme that reduces oxygen to superoxide, a precursor of microbicidal oxidants.
A301 or C8166 lymphoblastoid cell lines and X91(0) CGD EBV-transformed B lymphocytes have barely detectable NADPH oxidase activity or cytochrome b558 content (P < 0.05 in all situations).
Reconstitution of NADPH oxidase activity in human X-linked chronic granulomatous disease myeloid cells after stable gene transfer using a recombinant adeno-associated virus 2 vector.
This paper deals with the mechanisms of activation of NADPH oxidase investigated using EBV-transformed human B lymphoblastoid cell lines (B cells) from normal subjects and from patients affected by X-linked chronic granulomatous disease (CGD).The results reported are as follows.
CGD is a primary immunodeficiency disease which results from the absence of the NADPH oxidase in the phagocytic cells, leading to recurrent pyogenic infection and granuloma and abscess formation.
An in-frame triplet deletion within the gp91-phox gene in an adult X-linked chronic granulomatous disease patient with residual NADPH-oxidase activity.
The bacteriocidal capacity of phagocytic cells is impaired in X-linked chronic granulomatous disease (X-CGD), a disorder characterized by the absence of functional plasma-membrane-associated NADPH oxidase.