{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:46:12Z","timestamp":1776858372852,"version":"3.51.2"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Hematopoietic stem cell transplantation (HSCT) is a curative treatment for pediatric hematologic and immunologic disorders, with successful immune reconstitution being critical for long-term survival. We report the unique case of persistent hypogammaglobulinemia following fully matched HSCT from a phenotypically normal sibling donor carrying a heterozygous\n                      <jats:italic>RAG1<\/jats:italic>\n                      gene mutation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A 13-year-old girl with EBV-associated NK\/T-cell lymphoproliferative disorder underwent fully matched sibling HSCT from her mutation-carrying donor. Whole-exome sequencing confirmed the\n                      <jats:italic>RAG1<\/jats:italic>\n                      c.994C&amp;gt;T (p.Arg332*) mutation in both donor and recipient. Post-transplant monitoring included serial lymphocyte subset measurements and immunoglobulin level monitoring over a 5-year period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Despite successful engraftment and quantitative T- and B-cell recovery, the patient developed persistent hypogammaglobulinemia. Serum IgG levels declined to below 4g\/L at 4 months post-HSCT and remained persistently below 2g\/L from 11 months onwards (with only one measurement of 2.57g\/L during this period). IgA levels remained consistently below 0.2g\/L, becoming undetectable by 11 months and remaining so. IgM levels dropped below the detection threshold at 2 months and demonstrated only partial recovery by 18 months (peak: 0.29g\/L). The patient experienced recurrent respiratory infections, necessitating long-term immunoglobulin replacement therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case demonstrates that heterozygous variants in genes critical for hematopoietic reconstitution (such as\n                      <jats:italic>RAG1<\/jats:italic>\n                      mutations) may still lead to significant immunodeficiency post-transplantation. Our findings strongly suggest that potential donors carrying such mutations require careful evaluation, with non-carrier donors being preferentially selected when available, especially in the context of HSCT.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1798445","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:07:03Z","timestamp":1776856023000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case report: Persistent hypogammaglobulinemia following hematopoietic stem cell transplantation from a sibling donor with heterozygous RAG1 mutation"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[{"name":"Pediatric Hematology Department, Quanzhou Maternal and Child Health Hospital (Quanzhou Children\u2019s Hospital)","place":["Quanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Department, Quanzhou Maternal and Child Health Hospital (Quanzhou Children\u2019s Hospital)","place":["Quanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijie","family":"Chen","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Department, Quanzhou Maternal and Child Health Hospital (Quanzhou Children\u2019s Hospital)","place":["Quanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiming","family":"Hong","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Department, Quanzhou Maternal and Child Health Hospital (Quanzhou Children\u2019s Hospital)","place":["Quanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2013.76","article-title":"Incidence and risk factors for hypogammaglobulinemia in pediatric patients following allo-SCT","volume":"48","author":"Frangoul","year":"2013","journal-title":"Bone Marrow Transplant"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anpede.2021.08.010","article-title":"Chronic hypogammaglobulinemia after allogeneic stem cell transplantation and their treatment with subcutaneous immunoglobulin in pediatric patients","volume":"97","author":"Serra","year":"2022","journal-title":"Pediatr (Engl Ed)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2017.05.005","article-title":"Humoral immune reconstitution kinetics after allogeneic hematopoietic stem cell transplantation in children: A maturation block of IgM memory B cells may lead to impaired antibody immune reconstitution","volume":"23","author":"Abdel-Azim","year":"2017","journal-title":"Biol Blood Marrow Transplant"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00507","article-title":"Immune reconstitution after allogeneic hematopoietic stem cell transplantation","volume":"7","author":"Ogonek","year":"2016","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.28","article-title":"Human RAG mutations: biochemistry and clinical implications","volume":"16","author":"Notarangelo","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1155380","article-title":"B cell abnormalities and autoantibody production in patients with partial RAG deficiency","volume":"14","author":"Min","year":"2023","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000831","article-title":"Donor selection in allogeneic stem cell transplantation","volume":"31","author":"Barriga","year":"2024","journal-title":"Curr Opin Hematol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00782","article-title":"B cell reconstitution and influencing factors after hematopoietic stem cell transplantation in children","volume":"10","author":"van der Maas","year":"2019","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1397567","article-title":"Case report: Persistent hypogammaglobulinemia and mixed chimerism after HLA class-II disparate-hematopoietic stem cell transplant","volume":"15","author":"de Gier","year":"2024","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"16012","DOI":"10.3390\/ijms242116012","article-title":"Persistent hypogammaglobulinemia after receiving rituximab post-HSCT is not caused by an intrinsic B cell defect","volume":"24","author":"Ott","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3038.2012.01339.x","article-title":"From severe combined immunodeficiency to Omenn syndrome after hematopoietic stem cell transplantation in a RAG1 deficient family","volume":"23","author":"Martinez-Martinez","year":"2012","journal-title":"Pediatr Allergy Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00808","article-title":"Family history of early infant death correlates with earlier age at diagnosis but not shorter time to diagnosis for severe combined immunodeficiency","volume":"8","author":"Luk","year":"2017","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.09.016","article-title":"Adult-onset manifestation of idiopathic T-cell lymphopenia due to a heterozygous RAG1 mutation","volume":"131","author":"Abraham","year":"2013","journal-title":"J Allergy Clin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1798445\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:07:08Z","timestamp":1776856028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1798445\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":13,"alternative-id":["10.3389\/fimmu.2026.1798445"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1798445","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]},"article-number":"1798445"}}