[Chronic-granulomatous disease].

Area of Science:

• Immunology
• Genetics
• Cell Biology

Background:

• Chronic-granulomatous disease (CGD) is a rare inherited primary immunodeficiency.
• It results from defective oxidative metabolism in phagocytic cells, leading to severe infections.
• The NADPH oxidase complex dysfunction is central to CGD pathogenesis.

Purpose of the Study:

• To summarize the understanding of CGD, its genetic basis, and clinical manifestations.
• To highlight the role of the NADPH oxidase complex, particularly Nox2.
• To discuss current management and future therapeutic strategies.

Main Methods:

• Review of existing literature on CGD genetics and pathophysiology.
• Analysis of clinical data differentiating X-linked and autosomal recessive forms.
• Evaluation of current treatment modalities and emerging therapies.

Main Results:

• X-linked CGD, caused by CYBB gene mutations (Nox2), is the most common and severe form.
• Autosomal recessive CGD forms, affecting other oxidase components, present with milder, later-onset symptoms.
• Long-term antibiotic prophylaxis is crucial for managing CGD infections.

Conclusions:

• CGD management requires lifelong vigilance against infections.
• Hematopoietic stem-cell transplantation and gene therapy represent promising future treatments for CGD.
• Understanding the genetic heterogeneity of CGD is key to personalized therapeutic approaches.