Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee

Published: April 15, 2025

This report provides an updated classification of inborn errors immunity (IEIs) involving 508 different genes and 17 phenocopies. Of these, we 67 novel monogenic defects 2 phenocopies due to neutralizing anti-cytokine autoantibodies or somatic mutations, which either have been discovered since the previous update (published June 2022) were reported earlier but recently confirmed and/or expanded. The new additions made after rigorous review genetic descriptions IEIs by International Union Immunological Societies (IUIS) Expert Committee using criteria established define IEI. Although similar pathogenic variants in one gene, terms both classes mutation (missense, nonsense, etc.) impact on protein function, can result a spectrum phenotypic manifestations, they are herein classified according most consistently phenotype. In addition, because single gene recognizable diseases gain loss such cases their clinical manifestations as distinct entry same table depending associated will serve valuable resource for immunologists geneticists involved molecular diagnosis individuals with heritable acquired immunological disorders. Moreover, expect this also all disciplines medicine, patients may be first seen rheumatologists, hematologists, allergists, dermatologists, neurologists, gastroenterologists, pulmonologists, upon presenting features. Finally, expanding known related causes human immune requires dissection underlying cellular mechanisms, reveals fundamental requirements specific genes, pathways, processes, even cell types. Such knowledge not only contribute improved patient management pave way development implementation therapies that target cause—rather than symptoms—of these conditions.

Language: Английский

The 2024 update of IUIS phenotypic classification of human inborn errors of immunity

Published: April 15, 2025

Here, we report the 2024 update of phenotypic classification by International Union Immunological Societies (IUIS) expert committee (EC) on inborn errors immunity (IEI), which accompanies and complements genotypic classification. The aim this is to help diagnosis for clinicians at bedside focuses clinical features basic laboratory phenotypes specific IEI. In update, 559 IEI are described, including 67 novel monogenic defects 2 new phenocopies. This presented in form decision trees when possible, with essential or immunological phenotype entries.

Language: Английский