{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:05:29Z","timestamp":1790661929133,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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>Background<\/jats:title>\n                    <jats:p>\n                      X-linked Hyper-IgM Syndrome (X-HIGM) is a primary immunodeficiency caused by pathogenic variants in\n                      <jats:italic>CD40L<\/jats:italic>\n                      . Loss of functional CD40 ligand interferes with T-cell\u2013dependent B-cell responses and immunoglobulin class-switch recombination, resulting in susceptibility to recurrent and opportunistic infections. Because\n                      <jats:italic>CD40L<\/jats:italic>\n                      is located on the X chromosome, X-HIGM is usually diagnosed in males. Symptomatic females are rare, and the clinical and immunological features of these patients have not been well defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We report a 4-year-old Chinese girl who developed disseminated Talaromyces marneffei infection and was subsequently diagnosed with X-HIGM. Her clinical history and laboratory findings were reviewed, and a comprehensive immunological evaluation was performed, including flow cytometric analysis. Genetic testing was carried out by next-generation sequencing, and the identified variant was confirmed by Sanger sequencing. The possible effect of the\n                      <jats:italic>CD40L<\/jats:italic>\n                      c.364 + 2T&amp;gt;A variant on RNA splicing was examined using the online AI tool RNA-Splicer. We also analyzed peripheral blood mononuclear cells (PBMCs) from the patient and an age- and sex-matched healthy control by single-cell RNA sequencing to further characterize abnormalities in peripheral immune-cell populations and their transcriptional profiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A previously undescribed heterozygous\n                      <jats:italic>CD40L<\/jats:italic>\n                      c.364 + 2T&amp;gt;A variant was identified in the patient and was confirmed to be\n                      <jats:italic>de novo<\/jats:italic>\n                      . Analysis of the PBMC transcriptomes showed differences across several immune-cell compartments. In particular, B-cell populations showed impaired programs related to maturation and immunoglobulin class switching, while alterations were also observed in T-cell developmental states. The proportions of several myeloid and dendritic-cell populations were reduced in the patient. In addition, cell\u2013cell communication analysis indicated changes in interactions among multiple immune-cell subsets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      We identified a\n                      <jats:italic>de novo<\/jats:italic>\n                      splice-site variant in\n                      <jats:italic>CD40L<\/jats:italic>\n                      G in a symptomatic female child with X-HIGM and disseminated T. marneffei infection. The clinical presentation and single-cell transcriptomic findings highlight the broad effects of\n                      <jats:italic>CD40L<\/jats:italic>\n                      deficiency on the peripheral immune system. This case adds a previously unreported\n                      <jats:italic>CD40L<\/jats:italic>\n                      G variant to the spectrum of genetic changes associated with X-HIGM and provides additional information on the immune abnormalities that may occur in symptomatic female patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1875082","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:50:01Z","timestamp":1790661001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["X-linked hyper IgM syndrome with a novel CD40-ligand gene mutation suffered from infection of Talaromyces marneffei"],"prefix":"10.3389","volume":"17","author":[{"given":"Juan","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, 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Department, Ordnance Industry Hygiene Research Institute, Xi\u2019an","place":["Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxin","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University","place":["Zunyi, China"]},{"name":"Guizhou Key Laboratory of Modern Traditional Chinese Medicine Creation, Zunyi Medical University","place":["Zunyi, China"]},{"name":"Key Laboratory of Basic Pharmacology, Ministry of Education, Zunyi Medical University","place":["Zunyi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiji","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University","place":["Zunyi, China"]},{"name":"Guizhou Key Laboratory of Modern Traditional Chinese Medicine Creation, Zunyi Medical University","place":["Zunyi, China"]},{"name":"Key Laboratory of Basic Pharmacology, Ministry of Education, Zunyi Medical 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