Inborn Errors of Immunity and Primary Immunodeficiency Disorders

Inborn errors of immunity, historically termed primary immunodeficiency disorders, encompass a diverse group of heritable conditions that compromise innate and adaptive immune function. These disorders arise from monogenic defects affecting gene products essential to host defence, immune regulation or lymphoid development. Clinically, they manifest as heightened susceptibility to infections, autoimmunity, autoinflammation, allergy and malignancy. Advances in next-generation sequencing have accelerated the discovery of novel gene defects, broadening the recognised phenotypic spectrum and revealing unexpected disease mechanisms. Precision therapies, including targeted small-molecule inhibitors, biologics and haematopoietic stem cell transplantation, have transformed management for many conditions. At the same time, an expanded classification now recognises more than 480 distinct entities, grouped by molecular pathway and clinical phenotype, facilitating diagnosis and aetiological investigation. Globally, these disorders carry a substantial burden in paediatric and adult populations alike, underscoring the importance of newborn screening, tailored genetic counselling and multidisciplinary care to improve outcomes and quality of life.

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Inborn Errors of Immunity and Primary Immunodeficiency Disorders publication trend

The graph below shows the total number of articles in inborn errors of immunity and primary immunodeficiency disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Inborn Errors of Immunity: Heritable monogenic defects that disrupt immune pathways, leading to immunodeficiency, autoimmunity or autoinflammation.

Primary Immunodeficiency Disorders: Traditional term for inherited defects of immune function, characterised by recurrent infections and immune dysregulation.

Monogenic: Caused by mutation in a single gene, often resulting in a clear inheritance pattern and mechanistic insight.

Next-Generation Sequencing: High-throughput DNA sequencing technology that enables rapid identification of genetic variants across the exome or genome.

Haematopoietic Stem Cell Transplantation: Curative therapy involving replacement of a patient’s defective immune system with healthy donor stem cells.

References

1. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. Journal of Clinical Immunology (2022).
2. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4–insufficient subjects. Journal of Allergy and Clinical Immunology (2018).
3. Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry. Frontiers in Immunology (2018).