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Monocyte function in patients with chronic granulomatous disease of childhood
Insights
Adults with atypical chronic granulomatous disease (CGD) show reduced but significant monocyte bacterial killing despite impaired oxidative metabolism. This suggests nonoxidative mechanisms contribute to fewer infections in atypical CGD patients.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by impaired neutrophil function.
- Some adults with CGD exhibit mild or atypical forms with reduced infection frequency despite neutrophil defects.
Purpose of the Study:
- To investigate monocyte function in adults with atypical CGD.
- To compare monocyte bactericidal activity and oxidative metabolism in atypical CGD, classic CGD, and healthy controls.
Main Methods:
- Monocyte bactericidal assays were performed on ingested organisms.
- Oxidative metabolism in monocytes was assessed.
- Comparisons were made between atypical CGD, classic CGD, and normal control groups.
Main Results:
- Monocytes from atypical CGD patients exhibited significant bactericidal activity (75.7%) against ingested organisms, higher than classic CGD (50.3%) but lower than normal controls (88.1%).
- Despite severe oxidative metabolic defects in both atypical and classic CGD monocytes, atypical CGD monocytes demonstrated notable killing capacity.
- A statistically significant difference was observed in bactericidal activity between atypical CGD monocytes and normal monocytes (p=0.007).
Conclusions:
- Differences in monocyte bactericidal activity may explain the lower infection rates in atypical CGD patients compared to classic CGD patients.
- The findings suggest the presence of effective nonoxidative bactericidal mechanisms in atypical CGD monocytes, compensating for oxidative defects.
Abstract:
Adults with chronic granulomatous disease of childhood (CGD) have been described who remain relatively free of infection despite markedly abnormal neutrophil function. Monocyte function in four adults with this mild or atypical CGD syndrome was examined and compared to that of normal controls and to that of two patients with the more severe or classic CGD syndrome. Monocytes from patients with atypical CGD killed 75.7% +/- 2.6% (mean +/- SEM) of ingested organisms at 30 min, while monocytes from the patients with classic CGD killed only 50.3% +/- 4.2% of bacteria (p less than 0.001). The difference in bactericidal activity between atypical CGD monocytes and normal monocytes was relatively small (75.7% +/- 2.6% versus 88.1% +/- 3.7%, respectively) but was statistically significant (p = 0.007). Monocytes from both atypical and classic CGD patients showed markedly impaired oxidative metabolism. Differences in monocyte bactericidal activity may explain why atypical CGD patients have fewer infections than classic CGD patients. The presence of nonoxidative bactericidal mechanisms in atypical CGD monocytes is suggested by the demonstration of bactericidal activity despite severe oxidative metabolic defects.