ArticleArteriosclerosis, thrombosis, and vascular biology2016
Antiendothelial αvβ3 Antibodies Are a Major Cause of Intracranial Bleeding in Fetal/Neonatal Alloimmune Thrombocytopenia.
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Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
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33 citing papers in PubMed, 92 citations in OpenAlex.
- High-resolution cryo-EM structure of integrin αIIbβ3 bound to disease-causing maternal HPA-1a antibody that blocks integrin activation.Science advances · 2026Article
- Unlocking the locking secret behind FNAlT.Blood · 2026Article
- Structural basis of HPA-1a alloimmunization in FNAIT and allosteric regulation of integrin conformation.Blood · 2026Article
- Altered glycosylation profile of anti-HPA-1a-specific antibodies: insights from a prospective fetal and neonatal alloimmune thrombocytopenia cohort.Haematologica · 2026Article
- New perspectives on fetal and neonatal alloimmune thrombocytopenia for obstetricians.Frontiers in immunology · 2026Review
- Improving prediction of fetal/neonatal intracranial hemorrhage in HPA-1a alloimmunized pregnancies to guide antenatal management: An observational cohort study.Acta obstetricia et gynecologica Scandinavica · 2025Observational
- Diagnosis and Management of Fetal and Neonatal Alloimmune Thrombocytopenia: An Update 2025.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- The potential role of the αVβ3 integrin receptor in placental biology and normal and complicated pregnancies.British journal of haematology · 2025Review
- Screening of pregnant women for foetal neonatal alloimmune thrombocytopenia: A cost-utility analysis.Vox sanguinis · 2025Article
- Antigen-specific immunotherapy for platelet alloimmune disorders.Human immunology · 2024Review
- Pregnancy and childbirth in patients with Glanzmann Thrombasthenia.British journal of haematology · 2024Review
- Does anti-HPA-1a affect birthweight in fetal and neonatal alloimmune thrombocytopenia?Pediatric blood & cancer · 2024Article
- Pregnant Women at Low Risk of Having a Child with Fetal and Neonatal Alloimmune Thrombocytopenia Do Not Require Treatment with Intravenous Immunoglobulin.Journal of clinical medicine · 2023Review
- Article
- Cellular surface plasmon resonance-based detection of anti-HPA-1a antibody glycosylation in fetal and neonatal alloimmune thrombocytopenia.Frontiers in immunology · 2023Article
- Prevention of Fetal/Neonatal Alloimmune Thrombocytopenia in Mice: Biochemical and Cell Biological Characterization of Isoforms of a Human Monoclonal Antibody.ImmunoHorizons · 2022Article
- Article
- Clinical characteristics of human platelet antigen (HPA)-1a and HPA-5b alloimmunised pregnancies and the association between platelet HPA-5b antibodies and symptomatic fetal neonatal alloimmune thrombocytopenia.British journal of haematology · 2021Article
- Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study.International journal of molecular sciences · 2021Observational
- Profiling the Genetic and Molecular Characteristics of Glanzmann Thrombasthenia: Can It Guide Current and Future Therapies?Journal of blood medicine · 2021Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Sentot SantosoFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.). sentot.santoso@immunologie.med.uni-giessen.de ulrich.sachs@med.uni-giessen.de.
Hevi WihadmadyatamiFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Tamam BakchoulFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Silke WerthFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Nadia Al-FakhriFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Gregor BeinFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Volker KiefelFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Jieqing ZhuFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Peter J NewmanFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Behnaz BayatFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.).
Ulrich J SachsFrom the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany (S.S., H.W., S.W., G.B., B.B., U.J.S.); Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia (H.W.); Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany (T.B.); Center for Transfusion Medicine and Hemotherapy (N.A.-F., U.J.S.) and German Center for Fetomaternal Incompatibility (DZFI) (G.B., U.J.S.), University Hospital Giessen and Marburg, Giessen, Germany; Institute for Transfusion Medicine, University of Rostock, Rostock, Germany (V.K.); and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (J.Z., P.J.N.). sentot.santoso@immunologie.med.uni-giessen.de ulrich.sachs@med.uni-giessen.de.
Universitas Gadjah Mada · IDUniversity of Giessen · DEUniversity of Rostock · DE
Funding
Transgenic/Knockout CoreP01HL044612 · NHLBI · VERSITI WISCONSIN, INC. · PI NEWMAN, PETER J · 1990 to 2015
$33.4MStructural Transition of Cellular Integrins and Applications ThereofR01HL131836 · NHLBI · VERSITI WISCONSIN, INC. · PI Jieqing Zhu · 2016 to 2026
$5.5MGeneration of alloantigen-specific Designer Platelets for diagnostic and investigative useR01HL130054 · NHLBI · VERSITI WISCONSIN, INC. · PI NEWMAN, PETER J · 2016 to 2017
$1.0MConformational regulation in integrin bidirectional transmembrane signalingR56HL122985 · NHLBI · VERSITI WISCONSIN, INC. · PI ZHU, JIEQING · 2015 to 2015
$418kNHLBI NIH HHS P01 HL044612NHLBI NIH HHS R01 HL130054NHLBI NIH HHS R01 HL131836NHLBI NIH HHS R56 HL122985
Abstract
objectiveFetal/neonatal alloimmune thrombocytopenia is a severe bleeding disorder, which can result in intracranial hemorrhage (ICH), leading to death or neurological sequelae. In whites, maternal anti-human platelet antigen-1a (HPA-1a) antibodies are responsible for the majority of cases. No predictive factors for ICH are available to guide prophylactic treatment during pregnancy. In this study, we investigated antibodies from mothers with ICH-positive fetal/neonatal alloimmune thrombocytopenia and with ICH-negative fetal/neonatal alloimmune thrombocytopenia to identify serological and functional differences between the groups. APPROACH AND
resultsIn an antigen capture assay, we observed a stronger binding of +ICH antibodies to endothelial cell (EC)-derived αvβ3. By absorption experiments, we subsequently identified anti-HPA-1a antibodies of anti-αvβ3 specificity in the +ICH but not in the -ICH cohort. Only the anti-αvβ3 subtype, but not the anti-β3 subtype, induced EC apoptosis of HPA-1a-positive ECs by caspase-3/7 activation, and mediated by reactive oxygen species. In addition, only the anti-αvβ3 subtype, but not the anti-β3 subtype, interfered with EC adhesion to vitronectin and with EC tube formation.
conclusionsWe conclude that the composition of the anti-HPA-1a antibody subtype(s) of the mother may determine whether ICH occurs. Analysis of anti-HPA-1a antibodies of the anti-αvβ3 subtype in maternal serum has potential in the diagnostic prediction of ICH development and may allow for modification of prophylactic treatment in fetal/neonatal alloimmune thrombocytopenia.
Indexed as
AnimalsAntibody SpecificityAntigens, Human PlateletApoptosisAutoantibodiesCase-Control StudiesCaspase 3Caspase 7Cell AdhesionCHO CellsCricetulusEndothelial CellsFemaleGestational AgeHumansHuman Umbilical Vein Endothelial CellsAntigens, Human PlateletAutoantibodiesCASP3 protein, humanCASP7 protein, humanCaspase 3Caspase 7Integrin alphaVbeta3Integrin beta3ITGB3 protein, humanReactive Oxygen Speciesantibodiesendothelial cellsintracranial hemorrhagesreactive oxygen speciesthrombocytopenia, neonatal alloimmune
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