A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis

• Published in: Current opinion in pediatrics Vol. 34; no. 6; p. 580
• Main Authors: Hernandez, Joseph D, Hsieh, Elena W Y
• Format: Journal Article
• Language: English
• Published: United States 01.12.2022
• Subjects: Homeostasis; Humans; Infant, Newborn; Interleukin-2 Receptor alpha Subunit; Receptors, Interleukin-2 - genetics; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - therapy; X-Linked Combined Immunodeficiency Diseases
• DOI: 10.1097/MOP.0000000000001181

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. 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. 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.