The Role of Antibodies against Endothelial Cells in Immune Mediated Thrombocytopenia

Alloimmunization against HPAs leading to bleeding disorders is not only important for Caucasians but also Asians, especially in multiethnic Malays. This evidence promotes HPA typing and the installation of a national donor registry to improve the quality of treatment in Asia. In Caucasians, the pathomechanism how intracranial bleeding caused by anti-HPA-1a occurs during pregnancy in FNAIT was unclear. In this study, we found a high prevalence of anti-HPA-1a antibodies reactive against endothelial v3 (type-E) in mothers with FNAIT. In vitro, we could demonstrate that this subtype impairs endothelial function, and interferes with angiogenesis, indicating that type-E antibodies are directly responsible for the development of ICH. Our study showed that type-E antibody can also be formed in type 1 GT patients receiving platelet transfusions. Similar to FNAIT, this antibody type impairs endothelial function as well as angiogenesis. Thus, the presence of type-E antibodies in pregnant GT mothers may also cause severe FNAIT. Our study with a modified monoclonal antibody, 813, showed that platelet clearance and endothelial dysfunction mediated by maternal anti-HPA-1a alloantibodies may be prevented by such an approach. This interesting approach may help us to prevent bleeding and ICH in the fetus during pregnancy. In the last study, we showed that characterization of new platelet alloantigens involved in FNAIT does not only broaden our diagnostic repertoire but also improves our knowledge about the involvement of other molecule components (such as carbohydrates) on the formation of platelet alloantigenic determinants. Altogether, this study does not only underline the importance of alloantibodies in platelet clearance, but also highlights the importance of endothelial-reactive alloantibodies in severe bleeding such as, ICH in FNAIT cases. This knowledge will promote further studies including the development of new diagnostic methods and new treatment strategies of alloimmune mediated disorders.