{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:21:25Z","timestamp":1787721685838,"version":"build-2784847793"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"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-immunoglobulin M (XHIGM) syndrome is a rare primary immunodeficiency caused by mutations in the CD40 ligand gene\n                      <jats:italic>(CD40LG)<\/jats:italic>\n                      , characterized by defective T-cell-dependent B-cell class-switch recombination. Patients typically present with recurrent infections in early childhood, but diagnosis is often delayed due to heterogeneous clinical manifestations and the fact that serum IgM levels may remain within the normal range in a significant proportion of patients. Here we report a case of XHIGM in an infant whose diagnostic journey began with recurrent lymphadenitis and culminated in life-threatening\n                      <jats:italic>Pneumocystis jirovecii<\/jats:italic>\n                      pneumonia (PJP).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 6-month-old male infant was admitted with severe respiratory distress and hypoxemia. He had recurrent axillary lymphadenitis at 1 and 2 months of age and significant failure to thrive. Chest CT showed bilateral consolidative and interstitial opacities. Immunological evaluation revealed markedly decreased IgA, normal IgM and IgG, and profound T-cell lymphopenia. Sputum metagenomic sequencing identified\n                      <jats:italic>Pneumocystis jirovecii<\/jats:italic>\n                      . Whole-genome sequencing identified a hemizygous likely pathogenic\n                      <jats:italic>CD40LG<\/jats:italic>\n                      mutation (NM_000074.3:c.520C&amp;gt;T, p.Q174*); his mother was a carrier. He was treated with mechanical ventilation, trimethoprim-sulfamethoxazole (TMP-SMX), micafungin, corticosteroids, and intravenous immunoglobulin (IVIG), and was discharged after 36 days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In infants with recurrent or opportunistic infections, persistently low IgA and declining T-cell counts\u2014even when initial screening appears normal\u2014should raise suspicion for underlying immunodeficiency and prompt genetic evaluation. Early aggressive management and evaluation for hematopoietic stem cell transplantation are essential to improve outcomes.<\/jats:p>\n                    <jats:p>Serial immunological evaluation is essential in infants with recurrent or opportunistic infections, as persistently low IgA and declining T-cell counts\u2014even when initial screening appears normal\u2014should prompt genetic evaluation for underlying immunodeficiency. Early aggressive management and evaluation for hematopoietic stem cell transplantation are essential to improve outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1929323","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:43:47Z","timestamp":1787719427000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["X-linked hyper-IgM syndrome presenting as severe Pneumocystis pneumonia in a 6-month-old infant: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Ying","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children\u2019s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu","place":["Sichuan, China"]},{"name":"Department of Pediatrics, WCSUH-Tianfu Sichuan Provincial Children\u2019s Hospital, Meishan","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children\u2019s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu","place":["Sichuan, China"]},{"name":"Department of Pediatrics, WCSUH-Tianfu Sichuan Provincial Children\u2019s Hospital, Meishan","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children\u2019s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu","place":["Sichuan, China"]},{"name":"Department of Pediatrics, WCSUH-Tianfu Sichuan Provincial Children\u2019s Hospital, Meishan","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children\u2019s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu","place":["Sichuan, China"]},{"name":"Department of Pediatrics, WCSUH-Tianfu Sichuan Provincial Children\u2019s Hospital, Meishan","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children\u2019s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu","place":["Sichuan, China"]},{"name":"Department of Pediatrics, WCSUH-Tianfu Sichuan Provincial Children\u2019s Hospital, Meishan","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children\u2019s Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu","place":["Sichuan, China"]},{"name":"Department of Pediatrics, WCSUH-Tianfu Sichuan Provincial Children\u2019s Hospital, Meishan","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1177\/1753425917739681","article-title":"Prospects for modulating the CD40\/CD40L pathway in the therapy of the hyper-IgM syndrome","volume":"24","author":"Meng","year":"2018","journal-title":"Innate Immun"},{"key":"B2","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1186\/s12887-022-03726-z","article-title":"Respiratory infections in X-linked hyper-IgM syndrome with CD40LG mutation: a case series of seven children in China","volume":"22","author":"Fan","year":"2022","journal-title":"BMC Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.clim.2018.11.007","article-title":"The hyper IgM syndromes: Epidemiology, pathogenesis, clinical manifestations, diagnosis and management","volume":"198","author":"Yazdani","year":"2019","journal-title":"Clin Immunol (Orlando Fla)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.eimc.2019.05.005","article-title":"Pneumocystis jirovecii pneumonia in children. 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