{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:36:27Z","timestamp":1768206987116,"version":"3.49.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but fatal blood transfusion complication, with a mortality rate of 90-100%. Severe combined immunodeficiency (SCID) is a life-threatening primary immunodeficiency with profound cellular and humoral defects. Patients with SCID are highly susceptible to TA-GVHD. Here, we report a 4-month-old male admitted for sepsis and severe pneumonia, with pustular rash and unhealed exudative Bacillus Calmette-Gu\u00e9rin vaccination site. Laboratory tests showed hypogammaglobulinemia and lymphopenia. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Mycobacterium bovis complex was detected in blood, while rifampicin-resistant Mycobacterium tuberculosis complex was identified in sputum and ascitic fluid. Whole-exome and Sanger sequencing identified a novel interleukin-2 receptor common gamma chain (IL2RG) nonsense mutation [NM_000206.3: c.865C&amp;gt;T, p.(Arg289Ter)]. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. On the 33rd day of admission, the infant accidentally received non-irradiated leucoreduced red blood cells, then developed typical TA-GVHD manifestations including fever, hepatomegaly, rash and diarrhea, and high-resolution Human Leukocyte Antigen typing confirmed it. The parents chose to terminate treatment on the 69th day of admission, and the patient died after discharge. The dynamic evolution of clinical manifestations and laboratory tests in this patient is described, along with a review of the relevant literature. This report expands the mutational spectrum of IL2RG and reveal the reference value of peripheral blood lymphocyte and eosinophil counts for early TA-GVHD identification.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1708366","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:40:15Z","timestamp":1768196415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Transfusion-associated graft-versus-host disease in severe combined immunodeficiency"],"prefix":"10.3389","volume":"16","author":[{"given":"Chunxue","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuewen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-01-620872","article-title":"A systematic review of transfusion-associated graft-versus-host disease","volume":"126","author":"Kopolovic","year":"2015","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/j.1423-0410.2008.01073.x","article-title":"Transfusion-associated graft-versus-host disease","volume":"95","author":"Dwyre","year":"2008","journal-title":"Vox Sang"},{"key":"B3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.tmrv.2008.09.006","article-title":"Transfusion-associated graft-versus-host disease","volume":"23","author":"R\u00fchl","year":"2009","journal-title":"Transfus Med Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/tme.12081","article-title":"Analysis of 66 patients definitive with transfusion-associated graft-versus-host disease and the effect of universal irradiation of blood","volume":"23","author":"Uchida","year":"2013","journal-title":"Transfus Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.1983.tb01937.x","article-title":"Human posttransfusion graft-versus-host disease","volume":"45","author":"Brubaker","year":"1983","journal-title":"Vox Sang"},{"key":"B6","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/s0887-7963(96)80121-0","article-title":"Survey of transfusion-associated graft-versus-host disease in immunocompetent recipients","volume":"10","author":"Ohto","year":"1996","journal-title":"Transfus Med Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2009.124","article-title":"Irradiation eradication and pathogen reduction. Ceasing cesium irradiation of blood products","volume":"44","author":"Mintz","year":"2009","journal-title":"Bone Marrow Transplant"},{"key":"B8","article-title":"Transfusion-associated graft-versus-host disease in severe combined immunodeficiency","volume":"20","author":"Sebnem Kilic","year":"2010","journal-title":"J Investig Allergol Clin Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196510282731803","article-title":"Aplastic anemia, histiocytosis and erythrodermia in immunologically deficient children. Probable human runt disease","volume":"273","author":"Hathaway","year":"1965","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3476(70)80291-8","article-title":"Thymic alymphoplasia, previously reported as dysgammaglobulinemia type I","volume":"76","author":"Cashman","year":"1970","journal-title":"J Pediatr"},{"key":"B11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1097\/00130478-200201000-00013","article-title":"Transfusion-associated graft versus host disease","volume":"3","author":"Parshuram","year":"2002","journal-title":"Pediatr Crit Care Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1453046","article-title":"X-linked severe combined immunodeficiency complicated by disseminated bacillus Calmette-Gu\u00e9rin disease caused by a novel pathogenic mutation in exon 3 of the IL2RG gene: a case report and literature review","volume":"15","author":"Jiang","year":"2024","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2005.10.011","article-title":"Transfusion-associated graft-versus-host disease","volume":"17","author":"Oto","year":"2006","journal-title":"Eur J Intern Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2010.03011.x","article-title":"How do we prevent transfusion-associated graft-versus-host disease in children","volume":"51","author":"King","year":"2011","journal-title":"Transfusion"},{"key":"B15","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/s0140-6736(68)91467-0","article-title":"Complement deficiency and chromosomalbreaks in a case of Swiss-type agammaglobulinaemia","volume":"1","author":"Jacobs","year":"1968","journal-title":"Lancet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1967.03130130041011","article-title":"Graft-vs-host reaction following a single blood transfusion","volume":"201","author":"Hathaway","year":"1967","journal-title":"JAMA"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(68)91468-2","article-title":"Immunological restitution in lymphopenic immunological deficiency syndrome","volume":"1","author":"Hong","year":"1968","journal-title":"Lancet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3476(69)80465-8","article-title":"Hereditary lymphopenic agammaglobulinemia associated with a distinctive form of short-limbed dwarfism and ectodermal dysplasia","volume":"75","author":"Gatti","year":"1969","journal-title":"J Pediatr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.1967.tb05519.x","article-title":"Familial autohemolytic anemia and runting syndrome with Rh-o-specific autoantibody","volume":"7","author":"Shapiro","year":"1967","journal-title":"Transfusion"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1973.tb08121.x","article-title":"Unusual combined immunodeficiency syndrome exhibiting kappa-IgD paraproteinemia, residual gutimmunity and graft-versus-host reaction after plasma infusion","volume":"62","author":"Rubinstein","year":"1973","journal-title":"Acta Paediatr Scand"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3476(66)80443-2","article-title":"Aplastic anemia and alymphocytosis in an infant with hypogammaglobulinemia: graft-versus-host reaction","volume":"68","author":"Hathaway","year":"1966","journal-title":"J Pediatr"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/BF00443203","article-title":"Graft-versus-host reaction after blood transfusion in a patient with cellular immunodeficiency: the role of histocompatibility testing","volume":"132","author":"Niethammer","year":"1979","journal-title":"Eur J Pediatr"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(63)91750-1","article-title":"Vaccinia gangrenosa due to hypogammaglobulinaemia","volume":"1","author":"White","year":"1963","journal-title":"Lancet"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/adc.46.248.571","article-title":"Partial immunodeficiency and graft-versus host disease","volume":"46","author":"Roberton","year":"1971","journal-title":"Arch Dis Child"},{"key":"B25","unstructured":"2023"},{"key":"B26","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/cei.13405","article-title":"The IL-2RG R328X nonsense mutation allows partial STAT-5 phosphorylation and defines a critical region involved in the leaky-SCID phenotype","volume":"200","author":"Arcas-Garc\u00eda","year":"2020","journal-title":"Clin Exp Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2025.1641956","article-title":"A novel de novo IL2RG nonsense mutation in a pediatric patient with X-linked severe combined immunodeficiency","volume":"16","author":"Wang","year":"2025","journal-title":"Front Genet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.713924","article-title":"Case report: reactive lymphohistiocytic proliferation in infant with a novel nonsense variant of IL2RG who received BCG vaccine","volume":"9","author":"Yahya","year":"2021","journal-title":"Front Pediatr"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/0955-3886(95)00000-n","article-title":"Transfusion-associated graft-versus-host disease: current concepts and future trends","volume":"16","author":"Seghatchian","year":"1995","journal-title":"Transfus Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4103\/hemoncstem.HEMONCSTEM-D-24-00043","article-title":"Transfusion-associated graft-versus-host disease (TA-GVHD) and graft-versus-host disease (GVHD): Pathophysiology and management (contrasted and compared)","volume":"17","author":"Valsami","year":"2024","journal-title":"Hematol Oncol Stem Cell Ther"},{"key":"B33","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1002\/iid3.25","article-title":"Eosinophils in the blood of hematopoietic stem cell transplanted patients are activated and have different molecular marker profiles in acute and chronic graft-versus-host disease","volume":"2","author":"Cromvik","year":"2014","journal-title":"Immun Inflammation Dis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2005.11.010","article-title":"Toward biomarkers for chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: III. Biomarker Working Group Report","volume":"12","author":"Schultz","year":"2006","journal-title":"Biol Blood Marrow Transplant"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2009.01.003","article-title":"Peripheral blood eosinophilia has a favorable prognostic impact on transplant outcomes after allogeneic peripheral blood stem cell transplantation","volume":"15","author":"Kim","year":"2009","journal-title":"Biol Blood Marrow Transplant"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1708366\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:40:37Z","timestamp":1768196437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1708366\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2025.1708366"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1708366","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"article-number":"1708366"}}