The role of antibodies against endothelial cells in immune mediated thrombocytopenia

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Alloimmunization against HPAs leading to bleeding disorders is significant not only for Caucasians but also for Asians, particularly in multiethnic Malays. This underscores the need for HPA typing and a national donor registry to enhance treatment quality in Asia. The pathomechanism behind intracranial bleeding caused by anti-HPA-1a during pregnancy in FNAIT has been unclear. Our study identified a high prevalence of anti-HPA-1a antibodies reactive against endothelial v3 (type-E) in mothers with FNAIT. In vitro, we demonstrated that this subtype impairs endothelial function and interferes with angiogenesis, indicating its direct role in developing ICH. Additionally, type-E antibodies can form in type 1 GT patients receiving platelet transfusions, similarly impairing endothelial function and angiogenesis, suggesting they may also cause severe FNAIT in pregnant GT mothers. Using a modified monoclonal antibody, 813, we found that maternal anti-HPA-1a alloantibodies could be prevented from causing platelet clearance and endothelial dysfunction. This approach may help avert bleeding and ICH in fetuses during pregnancy. Furthermore, characterizing new platelet alloantigens involved in FNAIT broadens our diagnostic capabilities and enhances our understanding of other molecular components in platelet alloantigen formation. This study emphasizes the critical role of alloantibodies in platelet clearance and severe bleeding, paving the w