2026-10-13T22:55:08Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33719029 2026-09-14T05:40:33Z category_696 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Tissue-nonspecific alkaline phosphatase deficiency is associated with altered immune cell profiles in hypophosphatasia.docx Luis Martínez-Heredia (17722704) Manuel Muñoz-Torres (695278) Trinidad González-Cejudo (17722710) María Dolores López-Robles (24868414) Mónica Cabeo (24868417) Ángel Carazo-Gallego (24868420) Enrique García-Recio (24868423) Sheila González-Salvatierra (17722716) Victoria Contreras-Bolívar (17722713) María Carmen Andreo-López (24868426) Iván Iglesias-Baena (261499) Francisco Andújar-Vera (5435450) Cristina García-Fontana (133781) Beatriz García-Fontana (2221810) Genetic Immunology calprotectin flow cytometry hypophosphatasia immune-mediated inflammatory diseases TNSALP Background<p>Hypophosphatasia (HPP) is a rare metabolic disorder caused by mutations in the ALPL gene leading to tissue-nonspecific alkaline phosphatase (TNSALP) deficiency. Although traditionally considered a skeletal disease, emerging evidence suggests an immunomodulatory role for TNSALP in systemic inflammation and immune-mediated inflammatory diseases (IMIDs). This study investigated clinical, biochemical, and immunological features associated with inflammation in HPP.</p>Methods<p>Forty-seven genetically confirmed HPP patients and 30 healthy controls with a comparable age and sex distribution were evaluated. Analyses included serum alkaline phosphatase (ALP), bone-specific ALP (BALP), C-reactive protein (CRP), fecal calprotectin (FCP), and flow cytometry in a subset of 29 HPP patients and 26 controls to assess leukocyte subpopulations and TNSALP expression, with confirmation by confocal microscopy.</p>Results<p>HPP patients exhibited reduced TNSALP expression in T cells, B cells, neutrophils, and monocytes, together with lower CD3 and CD8 fluorescence intensity and an increased CD16+/CD14+ monocyte ratio. IMIDs were frequent in this referral cohort and were associated with lower ALP and higher FCP. Within the flow-cytometry subset, lower proportions of CD8+ cells within the CD3−/CD19− NK-enriched population and of TNSALP+ B cells were associated with IMID status.</p>Discussion<p>These cross-sectional findings identify an association between TNSALP deficiency and a coordinated immune-inflammatory phenotype in HPP. They support the biological plausibility of an immunomodulatory role for TNSALP but do not establish that TNSALP deficiency causes inflammation or the development of IMIDs.</p> 2026-09-14T05:40:33Z Dataset Dataset 10.3389/fimmu.2026.1906557.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Tissue-nonspecific_alkaline_phosphatase_deficiency_is_associated_with_altered_immune_cell_profiles_in_hypophosphatasia_docx/33719029 CC BY 4.0