Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review.

Area of Science:

• Immunology
• Genetics
• Rare Diseases

Background:

• Hyper IgE syndromes (HIES) are rare primary immunodeficiencies characterized by recurrent infections, eczema, and high IgE levels.
• Genetic mutations in genes such as STAT3, IL6R, and PGM3 disrupt immune regulation and lead to HIES phenotypes.
• HIES presents with diverse clinical symptoms, making diagnosis and management challenging.

Purpose of the Study:

• To provide a comprehensive understanding of Hyper IgE syndromes.
• To review the latest updates on pathological features, clinical spectrum, and immunological abnormalities.
• To discuss inheritance patterns, new candidate genes, challenges, management, and future directions for HIES.

Main Methods:

• An extensive literature search was conducted across multiple databases (PubMed, Scopus, WHO, ClinVar).
• Preference was given to recently published articles to include the latest research.
• Relevant literature was meticulously reviewed to address the study's objectives.

Main Results:

• Common genetic variants in HIES include missense, nonsense, and frameshift mutations.
• Specific mutations are linked to distinct HIES subtypes, such as Hyper-IgE recurrent infection syndromes (IL6R, STAT3, ZNF341), Immunodeficiency 23 (PGM3), Netherton syndrome (SPINK5), and Loeys-Dietz syndrome (TGFBR).
• New genes and variants associated with HIES are continually being identified.

Conclusions:

• HIES significantly impacts patients due to complex manifestations and the need for lifelong management.
• Identifying causative genetic variants is essential for effective clinical management of HIES.
• Continued research into HIES pathophysiology and genetics offers hope for improved patient outcomes.