INTERLEUKIN-2 RECEPTOR γ CHAIN MUTATION RESULTS IN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY IN HUMANS

Abstract

Purpose of the Study. Interleukin-2 (IL-2) and IL-2 receptors play a critical role in the regulation of the T cell immune response. IL-2 receptors are made of combinations of three different chains a, β, and γ. Different combinations of these chains result in the formation of three different classes of IL-2 receptors. The authors of this paper were interested in the interleukin-2 receptor γ chain (IL-2Rγ) gene and its relationship to X-linked severe combined immunodeficiency (XSCID). Findings. The IL-2Rγ gene was localized to the X chromosome in the same region as the XSCID locus. The IL-2Rγ gene from three patients with XSCID were found to have point mutations leading to premature stop codons and truncated IL-2Rγ chains. These shortened IL-2Rγ chains lack the cytoplasmic domain required for cell signal transduction. Reviewers' Comments. This is the first article showing the XSCID is associated with mutations in the IL-2Rγ gene. This suggests that IL-2Rγ plays a critical role in the early development of T-cells and their function in the immune system. These results also suggest that other genetic defects in components of the IL-2/IL-2R system could be responsible for other forms of SCID or other immunodeficiency syndromes. The fact that all three patients had different mutations suggests that there is no single dominant mutation. These findings have important implications for prenatal and postnatal diagnosis, carrier identification, and possibly gene therapy for XSCID.