Chronic granulomatous disease

This is the first disease where a bone marrow transplant cured the patient

Elements of the case

• 15-yo male with a pulmonary fungus infection

• usually positive family history (X-linked); infections usually start sooner than 15 years of age

• WBC count normal

• normal T and B cells

• normal Ig levels

• WBC do not reduce NBT dye, which means that they don’t make phagolysosomes well

• so phagocytosis is normal but the killing function is not. granulomas result

• these people can’t kill all the organisms that other people can kill—Strep, Staph, etc.

Principles to understand

• phagocytosis, formation of phagolysosome

• generation of H₂O₂ by NADPH oxidase, then superoxide dismutase
  

• killing of phagocytosed organisms

• formation of granulomas when the above three things do not work

Neutrophil phagocytosis and activation

• “everybody is happy…except the organism”

Mechanisms of neutrophil killing

• defenses against pathogens include NO, antimicrobial peptides, competitors (steal iron from bugs)

NADPH oxidase schematic

• chronic granulomatous disease is a family of diseases. any number of the four different proteins in NADPH oxidase can be mutated

• gp91, however, is most commonly defective in CGD. it is a glycoprotein

• again, the phenotype is the same for a defect in any of the proteins

• you can tell which protein is defective if you look long enough at the family history

• don’t need to memorize this. if you want to, just remember that the biggest subunit is the one most commonly defective

Category: Pathology Notes