{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:40:58Z","timestamp":1786977658364,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T00:00:00Z","timestamp":1409184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["BMBF 01EO1303"],"award-info":[{"award-number":["BMBF 01EO1303"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EH 145\/6-1"],"award-info":[{"award-number":["EH 145\/6-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004702","name":"Baxter International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p>\n                    X\u2010linked severe combined immunodeficiency (X\u2010SCID) leads to a T\n                    <jats:sup>\u2212<\/jats:sup>\n                    NK\n                    <jats:sup>\u2212<\/jats:sup>\n                    B\n                    <jats:sup>+<\/jats:sup>\n                    immunophenotype and is caused by mutations in the gene encoding the IL\u20102 receptor \u03b3\u2010chain (IL2RG). IL2RG\n                    <jats:sup>R222C<\/jats:sup>\n                    leads to atypical SCID with a severe early onset phenotype despite largely normal NK\u2010 and T\u2010cell numbers. To address this discrepancy, we performed a detailed analysis of T, B, and NK cells, including quantitative STAT phosphorylation and functional responses to the cytokines IL\u20102, IL\u20104, IL\u201015, and IL\u201021 in a patient with the IL2RG\n                    <jats:sup>R222C<\/jats:sup>\n                    mutation. Moreover, we identified nine additional unpublished patients with the same mutations, all with a full SCID phenotype, and confirmed selected immunological observations. T\u2010cell development was variably affected, but led to borderline T\u2010cell receptor excision circle (TREC) levels and a normal repertoire. T cells showed moderately reduced proliferation, failing enhancement by IL\u20102. While NK\u2010cell development was normal, IL\u20102 enhancement of NK\u2010cell degranulation and IL\u201015\u2010induced cytokine production were absent. IL\u20102 or IL\u201021 failed to enhance B\u2010cell proliferation and plasmablast differentiation. These functional alterations were reflected by a differential impact of IL2RG\n                    <jats:sup>R222C<\/jats:sup>\n                    on cytokine signal transduction, with a gradient IL\u20104&lt;IL\u20102\/IL\u201015&lt;IL\u201021. Thus, IL2RG\n                    <jats:sup>R222C<\/jats:sup>\n                    causes a consistently severe clinical phenotype that is not predicted by the variable and moderate impairment of T\u2010cell immunity or TREC analysis.\n                  <\/jats:p>","DOI":"10.1002\/eji.201444689","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T13:46:54Z","timestamp":1405432014000},"page":"3129-3140","source":"Crossref","is-referenced-by-count":35,"title":["Patients with T\n                    <sup>+\/low<\/sup>\n                    NK\n                    <sup>+<\/sup>\n                    IL\u20102 receptor \u03b3 chain deficiency have differentially\u2010impaired cytokine signaling resulting in severe combined immunodeficiency"],"prefix":"10.1002","volume":"44","author":[{"given":"Sebastian","family":"Fuchs","sequence":"first","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) University Medical Center and University of Freiburg  Freiburg Germany"},{"name":"Faculty of Biology University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Rensing\u2010Ehl","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) University Medical Center and University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Erlacher","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) University Medical Center and University of Freiburg  Freiburg Germany"},{"name":"Center of Pediatric and Adolescent Medicine University Medical Center  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vraetz","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) University Medical Center and University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Hartjes","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) University Medical Center and University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ales","family":"Janda","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) University Medical Center and University of Freiburg  Freiburg Germany"},{"name":"Center of Pediatric and Adolescent Medicine University Medical Center  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) University Medical Center and University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam R.","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Gilmour","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Institute of Child Health (ICH) University College London (UCL)  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"de Saint\u2010Basile","sequence":"additional","affiliation":[{"name":"INSEM UMR 1163 Laboratory of Normal and Pathological Homeostasis of the Immune System  Paris France"},{"name":"Paris Descartes\u2010Sorbonne Paris Cit\u00e9 University Imagine Institute  Paris France"},{"name":"Centre d'Etudes des D\u00e9ficits Immunitaires, Assistance Publique\u2010H\u00f4pitaux de Paris H\u00f4pital Necker  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaim M.","family":"Roifman","sequence":"additional","affiliation":[{"name":"The Canadian Centre for Primary Immunodeficiency Division of Immunology and Allergy and Department of Pediatrics the Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency the Hospital for Sick Children and the University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Cheuk","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency (CCI) University Medical Center and University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Gennery","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, 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