Hyper-IgE in the allergy clinic--when is it primary immunodeficiency?

Area of Science:

• Immunology
• Genetics
• Allergy

Background:

• The 2017 International Union of Immunological Societies (IUIS) classification identifies three hyper-IgE syndromes (HIES): Job's syndrome (STAT3-loss of function), PGM3, and SPINK5 syndromes.
• Primary immunodeficiency (PID) diagnosis is challenging due to rarity, leading to delays and poorer outcomes.
• Extreme serum IgE elevation is linked to various PID syndromes, including novel CARD11 and ZNF341 deficiencies.

Purpose of the Study:

• To update clinicians on recent advancements at the allergy-immunodeficiency interface.
• To highlight clinical scenarios suggesting immunodeficiency with extreme high IgE.
• To outline initial laboratory assessment and management strategies.

Main Methods:

• Literature review of recent developments in hyper-IgE syndromes and PID.
• Analysis of clinical presentations associated with extreme IgE elevation.
• Synthesis of current diagnostic and management approaches.

Main Results:

• Extreme IgE elevation is associated with multiple PID syndromes beyond the established HIES.
• Novel genetic deficiencies (e.g., CARD11, ZNF341) are increasingly recognized.
• Barrier defects can mimic PID with high IgE.

Conclusions:

• Awareness of genetic testing implications and limitations is vital for clinicians.
• Prompt recognition of clinical clues for PID with extreme IgE is essential for timely intervention.
• Integrated management of allergy and immunodeficiency is critical for improved patient prognosis.