{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:45:34Z","timestamp":1790477134774,"version":"4.1.0"},"reference-count":75,"publisher":"American Society of Hematology","issue":"18","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare but life-threatening condition in which maternal alloantibodies, generated during pregnancy, target human platelet antigens (HPAs), leading to thrombocytopenia and increased risk of bleedings in the fetus or neonate. The most clinically relevant antigen in people of European descent is HPA-1a, located on the integrin \u03b23 subunit. The \u03b23 integrins are conformationally regulated heterodimeric receptors including platelet integrin \u03b1IIb\u03b23 but also \u03b1v\u03b23, expressed strongly on endothelial cells. FNAIT is clinically highly heterogeneous, with symptoms ranging from mild thrombocytopenia to intracranial hemorrhage (ICH), which can cause lifelong disabilities or perinatal death. It has been suggested that anti\u2013HPA-1a antibodies that exclusively react with \u03b1v\u03b23 cause ICH, due to induction of endothelial cell damage and\/or defects in angiogenesis. Here, we analyzed a large cohort of retrospectively and prospectively collected maternal sera from severe and mild FNAIT cases. Disease severity was associated with the extent of thrombocytopenia, and with high anti\u2013HPA-1a antibody reactivity toward both \u03b1IIb\u03b23 and \u03b1v\u03b23. Exclusive anti\u2013HPA-1a reactivity with \u03b1v\u03b23 or endothelial cells was not found. In contrast, all anti\u2013HPA-1a antibodies reacted with platelets and endothelial cells, and with \u03b1v\u03b23- and \u03b1IIb\u03b23-transduced cells, but reacted generally more with the \u03b1IIb\u03b23 integrin. Furthermore, HPA-1a epitope accessibility and antibody binding is influenced by integrin conformation and activation status. Higher reactivity of anti\u2013HPA-1a antibodies with \u03b1IIb\u03b23 over \u03b1v\u03b23 diminishes upon integrin conformational activation. Together, these data emphasize the need for further investigation into the relation between endothelial properties of anti\u2013HPA-1a antibodies and disease outcome in FNAIT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029618","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T19:04:54Z","timestamp":1754939094000},"page":"2189-2202","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":9,"title":["HPA-1a antibodies in FNAIT do not distinguish \u03b1v\u03b23 from \u03b1IIb\u03b23, and bind inactive integrins more strongly than active integrins"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6749-2594","authenticated-orcid":false,"given":"Janita J.","family":"Oosterhoff","sequence":"first","affiliation":[{"name":"1Sanquin Blood Supply Foundation, Department Research, Amsterdam, The Netherlands"},{"name":"2Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Stam","sequence":"additional","affiliation":[{"name":"3Institute of Biology, Division of Development & Disease, Leiden University, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3676-9503","authenticated-orcid":false,"given":"Suze R.","family":"van Brummelen","sequence":"additional","affiliation":[{"name":"1Sanquin Blood Supply Foundation, Department Research, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-554X","authenticated-orcid":false,"given":"Arthur E. H.","family":"Bentlage","sequence":"additional","affiliation":[{"name":"1Sanquin Blood Supply Foundation, Department Research, Amsterdam, The Netherlands"},{"name":"2Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thijs","family":"de Vos","sequence":"additional","affiliation":[{"name":"1Sanquin Blood Supply Foundation, Department Research, Amsterdam, The Netherlands"},{"name":"4Division of Neonatology, Department of Pediatrics, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8912-6739","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"de Pereda","sequence":"additional","affiliation":[{"name":"5Centro de Investigaci\u00f3n del C\u00e1ncer and Instituto de Biolog\u00eda Molecular y Celular del C\u00e1ncer, Consejo Superior de Investigaciones Cient\u00edficas, Universidad de Salamanca, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leendert","family":"Porcelijn","sequence":"additional","affiliation":[{"name":"6Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1608-876X","authenticated-orcid":false,"given":"Rick","family":"Kapur","sequence":"additional","affiliation":[{"name":"1Sanquin Blood Supply Foundation, Department Research, Amsterdam, The Netherlands"},{"name":"7Amsterdam University Medical Centre, University of Amsterdam, Landsteiner Laboratory, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masja","family":"de Haas","sequence":"additional","affiliation":[{"name":"6Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Amsterdam, The Netherlands"},{"name":"8Department of Haematology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Ellen","family":"van der Schoot","sequence":"additional","affiliation":[{"name":"1Sanquin Blood Supply Foundation, Department Research, Amsterdam, The Netherlands"},{"name":"7Amsterdam University Medical Centre, University of Amsterdam, Landsteiner Laboratory, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-003X","authenticated-orcid":false,"given":"Gestur","family":"Vidarsson","sequence":"additional","affiliation":[{"name":"1Sanquin Blood Supply Foundation, Department Research, Amsterdam, The Netherlands"},{"name":"2Department of Biomolecular Mass Spectrometry and Proteomics, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coert","family":"Margadant","sequence":"additional","affiliation":[{"name":"3Institute of Biology, Division of Development & Disease, 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