{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T21:58:25Z","timestamp":1775253505090,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Italian Ministry of Health to CC","award":["NET-2011-02350069"],"award-info":[{"award-number":["NET-2011-02350069"]}]},{"name":"Italian Ministry of Health to CC","award":["NET-2011-02350069"],"award-info":[{"award-number":["NET-2011-02350069"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>X-linked severe combined immunodeficiency (X-SCID) caused by full mutation of the IL2RG gene leads to T\u2212 B+ NK\u2212 phenotype and is usually associated with severe opportunistic infections, diarrhea, and failure to thrive. When IL2RG hypomorphic mutation occurs, diagnosis could be delayed and challenging since only moderate reduction of T and NK cells may be present. Here, we explored phenotypic insights and the impact of the p.R222C hypomorphic mutation (IL2RGR222C) in distinct cell subsets in an 8-month-old patient with atypical X-SCID. We found reduced CD4+ T cell counts, a decreased frequency of na\u00efve CD4+ and CD8+ T cells, and an expansion of B cells. Ex vivo STAT5 phosphorylation was impaired in CD4+CD45RO+ T cells, yet compensated by supraphysiological doses of IL-2. Sanger sequencing on purified cell subsets showed a partial reversion of the mutation in total CD3+ cells, specifically in recent thymic emigrants (RTE), effector memory (EM), and CD45RA+ terminally differentiated EM (EMRA) CD4+ T cells. Of note, patient\u2019s NK cells had a normal frequency compared to age-matched healthy subjects, but displayed an expansion of CD56bright cells with higher perforin content and cytotoxic potential, associated with accumulation of NK-cell stimulatory cytokines (IL-2, IL-7, IL-15). Overall, this report highlights an alteration in the NK-cell compartment that, together with the high disease-phenotype variability, should be considered in the suspicion of X-SCID with hypomorphic IL2RG mutation.<\/jats:p>","DOI":"10.1002\/jlb.5ma0220-239r","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T23:37:50Z","timestamp":1589240270000},"page":"739-748","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Partial T cell defects and expanded CD56bright NK cells in an SCID patient carrying hypomorphic mutation in the <i>IL2RG<\/i> gene"],"prefix":"10.1093","volume":"108","author":[{"given":"Cristina","family":"Cifaldi","sequence":"first","affiliation":[{"name":"Unit of Immune and Infectious Diseases, Academic Department of Pediatrics, Bambino Ges\u00f9 Childrens\u2019 Hospital-Scientific Institute for Research and Healthcare (IRCCS) , Rome , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Cotugno","sequence":"additional","affiliation":[{"name":"Research Unit of Congenital and Perinatal Infection, Academic Department of Pediatrics, Bambino Ges\u00f9 Childrens\u2019 Hospital-Scientific Institute for Research and Healthcare (IRCCS) , Rome , Italy"},{"name":"Department of Systems Medicine, University of Rome Tor Vergata , Rome , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Di Cesare","sequence":"additional","affiliation":[{"name":"Unit of Immune and Infectious Diseases, Academic Department of Pediatrics, Bambino Ges\u00f9 Childrens\u2019 Hospital-Scientific Institute for Research and Healthcare (IRCCS) , Rome , Italy"},{"name":"Department of Systems Medicine, University of Rome Tor Vergata , Rome , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Giliani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, A. Nocivelli Institute for Molecular Medicine, University of Brescia , Brescia , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gigliola","family":"Di Matteo","sequence":"additional","affiliation":[{"name":"Unit of Immune and Infectious Diseases, Academic Department of Pediatrics, Bambino Ges\u00f9 Childrens\u2019 Hospital-Scientific Institute for Research and Healthcare (IRCCS) , Rome , Italy"},{"name":"Department of Systems Medicine, University of Rome Tor Vergata , Rome , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donato","family":"Amodio","sequence":"additional","affiliation":[{"name":"Unit of Immune and Infectious Diseases, Academic Department of Pediatrics, Bambino Ges\u00f9 Childrens\u2019 Hospital-Scientific Institute for Research and Healthcare (IRCCS) , Rome , Italy"},{"name":"Department of Systems Medicine, University of Rome Tor Vergata , Rome , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Piano Mortari","sequence":"additional","affiliation":[{"name":"Immunology Research Division, Bambino Ges\u00f9 Childrens\u2019 Hospital IRCCS , Rome , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Chiriaco","sequence":"additional","affiliation":[{"name":"Unit of Immune and Infectious Diseases, Academic Department of Pediatrics, Bambino Ges\u00f9 Childrens\u2019 Hospital-Scientific Institute for Research and Healthcare (IRCCS) , Rome , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danilo","family":"Buonsenso","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. 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