The molecular basis of chronic granulomatous disease.

Abstract

CGD is a rare inherited immunodeficiency syndrome, caused by the phagocytes' inability to produce (sufficient) reactive oxygen metabolites. This dysfunction is due to a defect in the NADPH oxidase, the enzyme responsible for the production of superoxide. It is composed of several subunits, two of which, gp91phox and p22phox, form the membrane-bound cytochrome b558, while its three cytosolic components, p47phox, p67phox and p40phox, have to translocate to the membrane upon activation. This is a tightly and intricately controlled process that involves, among others, several low-molecular weight GTP-binding proteins. Gp91phox is encoded on the X-chromosome and p22phox, p47phox and p67phox on different autosomal chromosomes, and a defect in one of these components leads to CGD. This explains the variable mode of inheritance seen in this syndrome. Clinically CGD manifests itself typically already at a very young age with recurrent and serious infections, most often caused by catalase-positive pathogens. Modern treatment options, including prophylaxis with trimethoprim-sulfamethoxazole and rIFN-gamma as well as early and aggressive anti-infection therapy, have improved the prognosis of this disease dramatically. CGD, as a very well-characterized inherited affection of the hematopoietic stem cells, is predestined to be among the first diseases to profit from the advances in cutting-edge therapeutics, such as gene therapy and in utero stem cell transplantation.

• Authors: C Meischl, D Roos
• Journal: Springer seminars in immunopathology (Springer Semin Immunopathol) Vol. 19 Issue 4 Pg. 417-34 ( 1998) ISSN: 0344-4325 [Print] Germany
• PMID: 9618766 (Publication Type: Journal Article, Review)

Chemical References

• Membrane Glycoproteins
• Membrane Transport Proteins
• Phosphoproteins
• Recombinant Proteins
• Interferon-gamma
• CYBB protein, human
• NADPH Oxidase 2
• NADPH Oxidases
• CYBA protein, human
• neutrophil cytosolic factor 1
• NADPH Dehydrogenase

Topics

• Animals
• Disease Models, Animal
• Enzyme Activation
• Female
• Granulomatous Disease, Chronic (diagnosis, enzymology, genetics, immunology, therapy)
• Heterozygote
• Humans
• Interferon-gamma (therapeutic use)
• Membrane Glycoproteins (chemistry, genetics, metabolism)
• Membrane Transport Proteins
• Mice
• Mice, Knockout
• NADPH Dehydrogenase (chemistry, genetics, metabolism)
• NADPH Oxidase 2
• NADPH Oxidases (chemistry, metabolism)
• Phagocytes (enzymology, immunology)
• Phosphoproteins (genetics, metabolism)
• Pregnancy
• Prenatal Diagnosis
• Recombinant Proteins