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  • Review Article
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The impact of genetic immune disorders on infections including COVID-19, inflammatory bowel disease and cancer

Nature Immunology volume 26, pages 1440–1452 (2025)Cite this article

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Abstract

Inborn errors of immunity (IEIs) are rare genetic anomalies that cause defective immune function. Over 500 IEIs have been identified to date, affecting millions of patients globally. These IEIs reveal the complex interplay between genetics, the environment and microorganisms that determine immune disease phenotypes. Progress in understanding the molecular and cellular mechanisms of IEIs provides a genetic framework for a functional understanding of the human immune system, disease pathogenesis and successful therapeutic interventions. This Review describes how IEIs impact infectious diseases, particularly coronavirus disease 2019, inflammatory bowel disease and cancer.

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Fig. 1: Genetic causes of T cell deficiencies and associated infectious disease susceptibility.
Fig. 2: Genetic causes of B cell deficiencies and associated infectious disease susceptibility.
Fig. 3: Genetic causes of susceptibility to bacterial, fungal and viral infections.
Fig. 4: Monogenic IBD shares genes with IEI-associated IBD.

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Acknowledgements

A.Y.P., C.X., S.E.W., M.J.L. and J.C. are supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. A.O. is supported by the Marmara University, Scientific Research Projects Committee (BAPKO, ADEP program, grant no. 10788).

Author information

Author notes

  1. Michael J. Lenardo

    Present address: Calico Labs LLC, South San Francisco, CA, USA

  2. These authors contributed equally: Chen Xiang, Ann Y. Park.

  3. These authors jointly supervised this work: Ahmet Ozen, Jing Cui.

Authors and Affiliations

  1. Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Chen Xiang, Ann Y. Park, Sarah E. Weber, Michael J. Lenardo & Jing Cui

  2. Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Chen Xiang, Ann Y. Park, Sarah E. Weber, Michael J. Lenardo & Jing Cui

  3. Division of Allergy and Immunology, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey

    Ahmet Ozen

  4. Istanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey

    Ahmet Ozen

  5. The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey

    Ahmet Ozen

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  2. Ann Y. Park
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  3. Sarah E. Weber
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  4. Michael J. Lenardo
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  5. Ahmet Ozen
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  6. Jing Cui
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Contributions

The manuscript was written by C.X., A.Y.P., S.E.W., M.J.L., A.O. and J.C. Figures and tables were created by C.X., A.Y.P., A.O. and J.C. Supervision was carried out by A.O. and J.C. All authors reviewed and/or edited the paper before submission.

Corresponding authors

Correspondence to Ahmet Ozen or Jing Cui.

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Nature Immunology thanks Holm Uhlig, Evangelos Andreakos, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Laurie A. Dempsey, in collaboration with the Nature Immunology team.

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Supplementary information

Supplementary Tables 1 and 2

Supplementary Table 1: Categories of IEIs. Supplementary Table 2: Malignancy with IEIs.

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Xiang, C., Park, A.Y., Weber, S.E. et al. The impact of genetic immune disorders on infections including COVID-19, inflammatory bowel disease and cancer. Nat Immunol 26, 1440–1452 (2025). https://doi.org/10.1038/s41590-025-02225-4

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