Update on inborn errors of immunity

• Published in: Journal of allergy and clinical immunology Vol. 155; no. 3; pp. 740 - 751
• Main Authors: IJspeert, Hanna, Edwards, Emily S.J., O’Hehir, Robyn E., Dalm, Virgil A.S.H., van Zelm, Menno C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2025
• Subjects: COVID-19 - immunology; COVID-19 - prevention & control; diagnosis; gene therapy; hematopoietic stem cell transplantation; Humans; Immunologic Deficiency Syndromes - diagnosis; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Immunologic Deficiency Syndromes - therapy; Inborn errors of immunity; JAK inhibitor; Male; newborn screening; PI3K inhibitor; SARS-CoV-2 - immunology; STAT6; V(D)J recombination; Vaccination; PI3K inhibitor; SCID; COVID-19; SARS-CoV-2; PI3K; hematopoietic stem cell transplantation; JAK inhibitor; STAT6; CTLA-4; HSCT; NBS; CID; GOF; APDS; ACMG; OS; KREC; V(D)J recombination; IFN-I; diagnosis; gene therapy; Inborn errors of immunity; IEI; STAT; TACI; TREC; newborn screening
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2024.12.1075

Ever since the first description of an inherited immunodeficiency in 1952 in a boy with gammaglobulin deficiency, new insights have progressed rapidly in disorders that are now referred to as inborn errors of immunity. In a field where fundamental molecular biology, genetics, immune signaling, and clinical care are tightly intertwined, 2022-24 saw a multitude of advances. Here we report a selection of research updates with a main focus on (1) diagnosis and screening, (2) new genetic defects, (3) susceptibility to severe coronavirus disease 2019 infection and impact of vaccination, and (4) treatment. Importantly, new pathogenic insights more rapidly affect treatment outcomes, either through an earlier and more precise diagnosis or through implementation of novel, personalized treatment. The field is growing rapidly, so awareness, communication, and collaboration are key to improving treatment outcomes.