Anticytokine Autoantibodies and Fungal Infections

Area of Science:

• Immunology
• Infectious Diseases
• Genetics

Background:

• Adult-onset immunodeficiencies can mimic primary conditions.
• Severe fungal infections may indicate underlying immune dysregulation.
• Anticytokine autoantibodies (ACAAs) are increasingly recognized causes of acquired immunodeficiencies.

Purpose of the Study:

• To review the role of innate immunity and cytokines in fungal infections.
• To present clinical cases linking ACAAs to severe fungal infections.
• To discuss diagnostic testing and therapeutic strategies for ACAA-associated conditions.

Main Methods:

• Literature review on innate immunity and fungal infections.
• Case series analysis of four patients with ACAAs and severe fungal infections.
• Discussion of diagnostic assays for ACAAs and treatment options.

Main Results:

• Four distinct clinical scenarios are detailed: anti-interferon-γ with Talaromyces marneffei and histoplasmosis; anti-GM-CSF with Cryptococcus gattii; anti-IL-17A/F with mucocutaneous candidiasis.
• ACAAs were associated with refractory and severe fungal infections in these cases.
• The study highlights the importance of considering ACAAs in unexplained immunodeficiencies.

Conclusions:

• ACAAs can lead to severe, life-threatening fungal infections by impairing key cytokine pathways.
• Testing for ACAAs should be considered in patients with severe or recurrent fungal infections and immunodeficiency symptoms.
• Targeted therapies addressing both the infection and the autoantibody production are essential for management.