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Chronic Granulomatous Disease (CGD)

Clinical Features and Laboratory Testing



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Defect in the Innate Immune System: Chronic Granulomatous Disease

Slide 7

January 2010

Chronic Granulomatous Disease (CGD) is a classic example of a primary immunodeficiency affecting the innate immune system. This disease is genetically heterogeneous and caused by defects or mutations in the genes that encode the various subunits of the respiratory enzyme - NADPH oxidase, which on activation leads to the generation of hydrogen peroxide and superoxide that is bactericidal.

NADPH oxidase is composed of 6 subunits, 2 of which are membrane-bound - gp91phox or cytochrome B, encoded by the CYBB gene, and the gp22phox, encoded by the NCF2 gene. There are 3 cytosolic components - the p67phox, the p47phox and the p40phox encoded by the CYBA, NCF1 and NCF4 genes respectively. The G-protein, Rac-2 is also associated with the NADPH oxidase complex (and defects in the Rac-2 gene lead to a form of leukocyte-adhesion deficiency). The p40phox has not been shown to be associated with the pathogenesis of CGD and is thought to play a regulatory role in the NADPH oxidase activity, while all the remaining components are considered essential for the generation of the superoxide burst.

The NADPH oxidase components primarily function in electron transfer or translocation to, or stabilization of membrane components.

Gp91phox and p67phox are involved in electron transfer while p40phox and p47phox are associated with stabilization and translocation to the membrane.

Chronic Granulomatous Disease

 


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