{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:12:58Z","timestamp":1786464778853,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease. While autoimmunity is the leading cause of PAP in adults, the majority of pediatric cases occur secondary to immunodeficiency and opportunistic infections. Secondary PAP associated with CD40 ligand (CD40L) deficiency is extremely rare, and the underlying pathophysiology remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report the case of a 4-month-old boy admitted due to failure to thrive and severe hypoxemic respiratory failure. Chest computed tomography demonstrated diffuse ground-glass opacities with interlobular septal thickening. Bronchoalveolar lavage yielded clear fluid containing Periodic acid-Schiff-positive material consistent with PAP, and polymerase chain reaction was positive for\n                      <jats:italic>Pneumocystis jirovecii<\/jats:italic>\n                      . An immunologic evaluation showed hypogammaglobulinemia (IgG and IgA), a normal IgM level for his age, an absence of class-switched memory B cells, and significantly reduced CD40L expression on activated T lymphocytes. Targeted genetic testing identified a previously unreported hemizygous\n                      <jats:italic>CD40LG<\/jats:italic>\n                      missense variant [c.137T&amp;gt;C, p.(Leu46Pro)]. Integration of the patient\u2019s immunophenotype, an\n                      <jats:italic>in silico<\/jats:italic>\n                      variant evaluation, and segregation data permitted classification of this variant as likely pathogenic, confirming X-linked hyper-IgM syndrome. The patient improved with ventilatory support, high-dose trimethoprim-sulfamethoxazole, and immunoglobulin replacement therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Early-onset PAP associated with\n                      <jats:italic>P. jirovecii<\/jats:italic>\n                      infection may reveal CD40L deficiency and should prompt evaluation for primary immunodeficiency. An integrated clinico-immunologic assessment coupled with genetic testing is essential to provide a molecular diagnosis, guide management, and prognostication, and to support timely consideration of curative hematopoietic stem cell transplantation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1913335","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T13:57:00Z","timestamp":1786456620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pulmonary alveolar proteinosis and Pneumocystis jirovecii infection in an infant with hyper-IgM syndrome caused by a novel CD40LG variant: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"C.","family":"Leclercq","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Olinger","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Caminoa","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Chatzis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Dumitriu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Froidure","sequence":"additional","affiliation":[{"name":"Pulmonology Department, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Smet","sequence":"additional","affiliation":[{"name":"Department of Immunology, Laboratoire Hospitalier Universitaire de Bruxelles \u2013 Universitair Laboratorium Brussel (LHUB-ULB), Universit\u00e9 Libre de Bruxelles (ULB)","place":["Brussels, Belgium"]},{"name":"Immunology Department, University Hospital Brugmann, Universit\u00e9 Libre de Bruxelles (ULB)","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Balbeur","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]},{"name":"Department of Pediatrics, Clinique Saint-Pierre","place":["Ottignies, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Corbisier","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]},{"name":"Pediatric Intensive Care Unit, Cliniques Universitaires Saint-Luc, UCLouvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"B1","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"},{"key":"B2","doi-asserted-by":"publisher","first-page":"100297","DOI":"10.1016\/j.jtauto.2025.100297","article-title":"Hyperimmunoglobulin syndromes: a review of HIGM, HIES, and HIDS","volume":"11","author":"Chen","year":"2025","journal-title":"Journal of Translational Autoimmunity"},{"key":"B3","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1007\/s10875-016-0291-4","article-title":"Hyper IgM syndrome: a report from the USIDNET registry","volume":"36","author":"Leven","year":"2016","journal-title":"J Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1093\/protein\/gzm004","article-title":"The structural basis of hyper IgM deficiency\u2014CD40L mutations. 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