• Sentot Santoso, Hevi Wihadmadyatami, Tamam Bakchoul, Silke Werth, Nadia Al-Fakhri, Gregor Bein, Volker Kiefel, Jieqing Zhu, Peter J Newman, Behnaz Bayat, and Ulrich J Sachs.
• From 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.
• Arterioscler. Thromb. Vasc. Biol. 2016 Aug 1; 36 (8): 1517-24.

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.© 2016 American Heart Association, Inc.

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