ALLERGY, IMMUNOLOGY AND RELATED DISORDERS: Edited by Jordan S. OrangeA great disturbance in the force: IL-2 receptor defects disrupt immune homeostasisHernandez, Joseph D.a; Hsieh, Elena W.Y.b,c Author Information aDivision of Allergy, Immunology and Rheumatology, Department of Pediatrics, School of Medicine, Stanford University, Lucile Packard Children's Hospital, Palo Alto, California bSection of Allergy and Immunology, Department of Pediatrics, School of Medicine, University of Colorado, Children's Hospital Colorado, Aurora cUniversity of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA Correspondence to Elena W.Y. Hsieh, MD, Associate Professor, Section of Allergy and Immunology, Department of Pediatrics, School of Medicine, University of Colorado, Children's Hospital Colorado, 12800 East 19th Avenue, Mail Stop 8333, Room P18-8117, Aurora, CO 80045, USA, Department of Immunology and Microbiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA. Tel: +1 303 724 9650; e-mail: [email protected] Current Opinion in Pediatrics: December 2022 - Volume 34 - Issue 6 - p 580-588 doi: 10.1097/MOP.0000000000001181 Buy Metrics Abstract Purpose of review The current review highlights how inborn errors of immunity (IEI) due to IL-2 receptor (IL-2R) subunit defects may result in children presenting with a wide variety of infectious and inflammatory presentations beyond typical X-linked severe combined immune deficiency (X-SCID) associated with IL-2Rγ. Recent findings Newborn screening has made diagnosis of typical SCID presenting with severe infections less common. Instead, infants are typically diagnosed in the first days of life when they appear healthy. Although earlier diagnosis has improved clinical outcomes for X-SCID, atypical SCID or other IEI not detected on newborn screening may present with more limited infectious presentations and/or profound immune dysregulation. Early management to prevent/control infections and reduce inflammatory complications is important for optimal outcomes of definitive therapies. Hematopoietic stem cell transplant (HSCT) is curative for IL-2Rα, IL-2Rβ, and IL-2Rγ defects, but gene therapy may yield comparable results for X-SCID. Summary Defects in IL-2R subunits present with infectious and inflammatory phenotypes that should raise clinician's concern for IEI. Immunophenotyping may support the suspicion for diagnosis, but ultimately genetic studies will confirm the diagnosis and enable family counseling. Management of infectious and inflammatory complications will determine the success of gene therapy or HSCT. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.