Primary immunodeficiencies underlying fungal infections

Area of Science:

• Immunology
• Infectious Diseases
• Genetics

Background:

• Primary immunodeficiencies (PIDs) are increasingly recognized as underlying causes of fungal infections.
• Fungal infections in children and young adults warrant investigation for underlying PIDs.

Purpose of the Study:

• To review PIDs associated with superficial and invasive fungal infections.
• To emphasize the link between specific fungal infections and corresponding single-gene inborn errors of immunity.
• To propose that unknown inborn errors of immunity may cause fungal infections in some patients.

Main Methods:

• Literature review of primary immunodeficiencies and fungal infections.
• Analysis of genetic defects associated with fungal disease susceptibility.
• Correlation of specific fungal infections with PIDs.

Main Results:

• PIDs like chronic granulomatous disease, severe congenital neutropenia, and leukocyte adhesion deficiency predispose to invasive aspergillosis and candidiasis.
• Inborn errors of interferon-γ immunity are linked to endemic mycoses.
• Defects in interleukin-17 and CARD9 immunity are associated with chronic mucocutaneous candidiasis and deep dermatophytosis, respectively.

Conclusions:

• Chronic mucocutaneous candidiasis, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can be caused by PIDs.
• Specific fungal infections suggest particular PIDs.
• Inborn errors of immunity should be investigated in pediatric and young adult patients with fungal diseases, particularly when risk factors are absent.