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Lookup NU author(s): Professor Sophie HambletonORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
This report provides an updated classification of inborn errors of immunity (IEIs) involving 508 different genes and 17 phenocopies. Of these, we report 67 novel monogenic defects and 2 phenocopies due to neutralizing anti-cytokine autoantibodies or somatic mutations, which either have been discovered since the previous update (published June 2022) or were reported earlier but have been recently confirmed and/or expanded. The new additions were made after rigorous review of new genetic descriptions of IEIs by the International Union of Immunological Societies (IUIS) Expert Committee using criteria established to define IEI. Although similar pathogenic variants in one gene, in terms of both classes of mutation (missense, nonsense, etc.) and impact on protein function, can result in a spectrum of phenotypic manifestations, they are herein classified according to the most consistently reported phenotype. In addition, because different variants in a single gene can result in recognizable diseases due to gain or loss of function, such cases are classified according to their clinical manifestations as a distinct entry in the same or a different table depending on the associated phenotype. This report will serve as a valuable resource for clinical immunologists and geneticists involved in the molecular diagnosis of individuals with heritable and acquired immunological disorders. Moreover, we expect this report to also serve as a valuable resource for all disciplines of medicine, since patients with IEIs may be first seen by rheumatologists, hematologists, allergists, dermatologists, neurologists, gastroenterologists, and pulmonologists, depending upon their spectrum of presenting clinical features. Finally, expanding the known monogenic and related causes of human immune diseases requires dissection of underlying cellular and molecular mechanisms, which reveals fundamental requirements for specific genes, pathways, processes, and even cell types. Such knowledge may not only contribute to improved patient diagnosis and management but also pave the way to the development and implementation of therapies that target the cause—rather than the symptoms—of these conditions
Author(s): Poli MC, Aksentijevich I, Bousfiha AA, Cunningham-Rundles C, Hambleton S, Klein C, Morio T, Picard C, Puel A, Rezaei N, Seppänen MRJ, Somech R, Su HC, Sullivan KE, Torgerson TR, Meyts I, Tangye SG
Publication type: Article
Publication status: Published
Journal: Journal of Human Immunity
Year: 2025
Volume: 1
Issue: 1
Print publication date: 05/05/2025
Online publication date: 15/04/2025
Acceptance date: 17/03/2025
Date deposited: 06/05/2025
ISSN (electronic): 3065-8993
Publisher: Rockefeller University Press
URL: https://doi.org/10.70962/jhi.20250003
DOI: 10.70962/jhi.20250003
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