Severe Combined Immunodeficiencies

Villa, Anna; Moshous, Despina; Villartay, Jean‐Pierre de; Notarangelo, Luigi D.; Candotti, Fabio

doi:10.1016/b978-0-12-405546-9.00004-2

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Section: Discussionmentioning

confidence: 99%

“…Typically, patients with genetic mutations of the IL2RG gene are classically characterized by the absence or severe reduction of T and NK cell numbers, as well as the presence of non-functional B cells ( 33 ), these mutations are mainly localized within the exons 3-5 ( 34 , 35 ). Missense mutations are the most common pathogenic changes observed, followed by nonsense variants and insertions/deletions ( 35 ). On the other hand, atypical clinical presentations of X-SCID have been also described in patients carrying missense mutations of IL2RG resulting in the expression of lower amounts of γc protein with conserved binding affinity for IL-2, or in its reduced interaction with JAK3, and thus impairing T cell activation ( 9 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

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Case Report: Interleukin-2 Receptor Common Gamma Chain Defect Presented as a Hyper-IgE Syndrome

et al. 2021

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X-linked severe combined immunodeficiency (X-SCID) is caused by mutations of IL2RG, the gene encoding the interleukin common gamma chain (IL-2Rγ or γc) of cytokine receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Hypomorphic mutations of IL2RG may cause combined immunodeficiencies with atypical clinical and immunological presentations. Here, we report a clinical, immunological, and functional characterization of a missense mutation in exon 1 (c.115G>A; p. Asp39Asn) of IL2RG in a 7-year-old boy. The patient suffered from recurrent sinopulmonary infections and refractory eczema. His total lymphocyte counts have remained normal despite skewed T cell subsets, with a pronounced serum IgE elevation. Surface expression of IL-2Rγ was reduced on his lymphocytes. Signal transducer and activator of transcription (STAT) phosphorylation in response to IL-2, IL-4, and IL-7 showed a partially preserved receptor function. T-cell proliferation in response to mitogens and anti-CD3/anti-CD28 monoclonal antibodies was significantly reduced. Further analysis revealed a decreased percentage of CD4+ T cells capable of secreting IFN-γ, but not IL-4 or IL-17. Studies on the functional consequences of IL-2Rγ variants are important to get more insight into the pathogenesis of atypical phenotypes which may lay the ground for novel therapeutic strategies.

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