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Review
. 2021 Dec 1;33(6):657-675.
doi: 10.1097/MOP.0000000000001075.

New primary immunodeficiencies 2021 context and future

Yesim Demirdag  1 , Ramsay Fuleihan  2 , Jordan S Orange  2   3 , Joyce E Yu  2
Affiliations
Review

New primary immunodeficiencies 2021 context and future

Yesim Demirdag et al. Curr Opin Pediatr. .

Abstract

Purpose of review: Primary immunodeficiency diseases (PIDs), also called inborn errors of immunity (IEI), are genetic disorders classically characterized by an increased susceptibility to infection and/or disruption in the regulation of an immunologic pathway. This review summarizes and highlights the new IEI disorders in the IUIS 2019 report and 2020 interim report and discusses the directions for the future management of PIDs.

Recent findings: Since 2017, the International Union of Immunologic Societies (IUIS) IEI committee has updated the IUIS classification of IEIs with 88 new gene defects and 75 new immune disorders. The increased utilization of genetic testing and advances in the strategic evaluation of genetic variants have identified, not only novel IEI disorders, but additional genetic causes for known IEI disorders. Investigation of potential immune susceptibilities during the ongoing COVID-19 pandemic suggests that defects in Type I interferon signalling may underlie more severe disease.

Summary: The rapid discovery of new IEIs reflects the growing trend of applying genetic testing modalities as part of medical diagnosis and management.In turn, elucidating the pathophysiology of these novel IEIs have enhanced our understanding of how genetic mutations can modulate the immune system and their consequential effect on human health and disease.

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References

    1. Casanova JL, Conley ME, Seligman SJ, et al. Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies. J Exp Med 2014; 211:2137–2149.
    1. Tangye SG, Al-Herz W, Bousfiha A, et al. Human inborn errors of immunity: 2019 update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2020; 40:24–64.
    1. Bousfiha A, Jeddane L, Picard C, et al. Human inborn errors of immunity: 2019 update of the IUIS Phenotypical Classification. J Clin Immunol 2020; 40:66–81.
    1. Tangye SG, Al-Herz W, Bousfiha A, et al. The ever-increasing array of novel inborn errors of immunity: an interim update by the IUIS Committee. J Clin Immunol 2021; 41:666–679.
    1. Hsu AP, Donkó A, Arrington ME, et al. Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects. Blood 2019; 133:1977–1988.