A 6-year-old female suffers from recurrent infections by Aspergillus species, Pseudomonas species, and Staphylococcus aureus. The patient’s neutrophils are examined in the laboratory and they fail to react during the nitroblue tetrazolium test. Which of the following is most likely dysfunctional in this patient?
1.Lymphocytes
2.Immunoglobulin class switching
3.Superoxide dismutase
4.Myeloperoxidase
5.Respiratory burst
sol:
The patient presented in the question stem has recurrent infections by catalase-producing organisms. This presentation is consistent with chronic granulomatous disease, characterized by dysfunction of the respiratory burst.
Chronic granulomatous disease (CGD) is caused by a deficiency of neutrophil NADPH oxidase. Normally, NADPH oxidase generates reactive oxygen species in the neutrophil which are converted to hydrogen peroxide (a strong antibacterial chemical), in a series of reactions known as the respiratory burst. Patients with CGD are defenseless against those organisms that break down their own hydrogen peroxide, otherwise known as catalase-producing organisms. These include S. aureus, Pseudomonas, Serratia marescens, Nocardia, and Aspergillus - thus infections with these organisms are commonly seen in those with CGD. The nitroblue tetrazolium (NBT) test is the classic test for CGD. In patients with CGD, neutrophils FAIL to turn blue when exposed to nitroblue tetrazolium.
Illustration A shows the NBT test result. At left in Panel A, the neutrophils stain blue (negative for CGD). At right, the photo shows neutrophils that fail to turn blue (positive for CGD, negative NBT test).