{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T20:16:06Z","timestamp":1783023366959,"version":"3.54.6"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Discovery"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    X\u2010linked hypophosphatemia (XLH) is a rare hereditary disorder characterized by\n                    <jats:italic>PHEX<\/jats:italic>\n                    gene mutations, elevated\n                    <jats:italic>FGF23<\/jats:italic>\n                    levels, and impaired bone mineralization. Burosumab, a monoclonal antibody targeting\n                    <jats:italic>FGF23<\/jats:italic>\n                    , has demonstrated clinical efficacy; however, the immunological dynamics during treatment remain unexplored. This study employed longitudinal single\u2010cell RNA sequencing (scRNA\u2010seq) to characterize peripheral blood immune cell alterations across multiple treatment stages in pediatric XLH. We performed scRNA\u2010seq on peripheral blood mononuclear cells from pediatric patients with XLH at five time points spanning pretreatment and burosumab therapy phases, along with healthy pediatric controls. A total of 93,112 cells were analyzed using comprehensive bioinformatic pipelines, including unsupervised clustering, pseudotime trajectory analysis, temporal gene expression profiling, and cell\u2013cell communication inference. Eleven major immune cell populations were identified, with notable dynamic alterations in T cells and natural killer (NK) cell subtypes across treatment stages. The cellular proportion of T helper 2 (Th2) cells and regulatory T (Treg) cells were elevated before treatment and normalized during therapy, whereas T helper 17 (Th17) cells exhibited reciprocal patterns. Genes upregulated in Treg cells during early treatment were enriched in osteoclast differentiation pathway. Natural killer subtype 2\u00a0cells showed enrichment in osteoclast differentiation and interleukin\u201012 response pathways. Cell\u2013cell communication analysis identified dynamic interactions among Th2 cells, Th17 cells, Treg cells, and NK cell subtypes mediated by KLRB1\u2013CLEC2D and SELL\u2013SELPLG ligand\u2010receptor pairs. This longitudinal transcriptomic study provides the first comprehensive characterization of peripheral immune dynamics during burosumab therapy in XLH, offering new insights into the immunological mechanisms underlying treatment response.\n                  <\/jats:p>","DOI":"10.1002\/pdi3.70053","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T09:05:41Z","timestamp":1782551141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Single\u2010Cell Transcriptomic Profiling Reveals Dynamic Immune Cell Alterations During Burosumab Therapy in X\u2010Linked Hypophosphatemia"],"prefix":"10.1002","volume":"4","author":[{"given":"Yue","family":"Xie","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Pediatric Research Institute, Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Department of Endocrinology, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Department of Endocrinology, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Sun","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Pediatric Research Institute, Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Child Development and 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