title: An interleukin-2 receptor gamma chain mutation with normal thymus morphology.
abstract: One of the most common human immunodeficiencies is an X-linked condition arising from mutations of the gamma subunit of the interleukin-2 receptor (IL-2Rgamma). The IL-2Rgamma protein is one chain of the heterotrimeric (alpha, beta, gamma) IL-2 receptor, but also participates in the formation of the IL-4, 7, 9, and 15 receptor complexes. The diagnosis of X-linked SCID is usually relatively simple due to the distinctive immunological presentation; IL-2Rgamma-deficient patients typically lacking mature T lymphocytes (T-B+). However, it is becoming clear that this merely represents one extreme of a potential range of clinical presentations. We describe here a novel mutation of the human IL-2Rgamma chain (R222C) resulting in an unusual immunological phenotype. Although clinically immunodeficient, this patient has normal numbers of peripheral T and B cells, responds normally to mitogenic stimuli, and unusually, has a normal thymus gland. This IL-2Rgamma mutation is distinctive in that the protein is sufficiently stable to be expressed at the cell surface. While the T cell receptor repertoire appears complete, suggesting normal T cell differentiation occurs, patient T cells demonstrate a reduced ability to bind IL-2 and this appears sufficient to cause a deficiency in their ability to participate in antigenic responses. Early clinical recognition of this phenotype is critical as a delay in diagnosis may result in a fatal infection.
authors.affiliation: Division of Immunology and Allergy, Department of Pediatrics, Hospital for Sick Children and the University of Toronto, Toronto, Canada M5G 1X8.
authors.forename: N
authors.initials: N
authors.lastname: Sharfe
authors.forename: M
authors.initials: M
authors.lastname: Shahar
authors.forename: C M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000818:Animals; D019556:COS Cells; D006801:Humans; D007223:Infant; D053616:Janus Kinase 3; D008024:Ligands; D008297:Male; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology*
chemical_list: D008024:Ligands; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3