Selected inborn errors of immunity associated with severe atopic phenotypes: Implications for the practicing...

Area of Science:

• Immunology
• Genetics
• Allergy and Immunology

Background:

• Inborn errors of immunity (IEIs) encompass immune dysregulation beyond infection susceptibility, including autoimmunity, autoinflammation, and severe atopy.
• Food allergies and IEIs were historically distinct but share overlapping immune mechanisms, complicating the management of immune deficiencies.

Purpose of the Study:

• To investigate shared immunologic mechanisms between food allergies and IEIs.
• Focus on immune dysregulation, barrier defects, microbial dysbiosis, and regulatory T cell (Treg) function.

Main Methods:

• Comprehensive literature review using PubMed with keywords: food allergy, primary immunodeficiency, IEI, Treg cells, immune dysregulation, autoimmunity, autoinflammation, epithelial barrier dysfunction, microbiome.
• Prioritized studies on monogenic IEIs with severe allergic phenotypes and elevated IgE.
• Included original research, systematic reviews, meta-analyses, and historical studies.

Main Results:

• Allergic symptoms, including food allergy, often manifest early in IEIs, sometimes preceding infection susceptibility.
• Commonalities include Treg dysfunction, cytokine signaling defects, epithelial barrier compromise, and microbiome alterations.
• These findings have improved diagnosis and led to targeted therapies like biologics and gene therapy.

Conclusions:

• Regulatory T cells (Tregs) are crucial for immune tolerance in allergic, autoimmune, and immunodeficient conditions.
• Understanding immune dysregulation and barrier defects drives personalized treatment strategies for patients with both food allergy and IEIs.