Antigen-specific immunotherapy for platelet alloimmune disorders

Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) is a significant hematologic disorder arising from maternal immune responses to fetal platelet alloantigens, predominantly Human Platelet Antigen (HPA)-1a. This review first describes the pathogenesis of FNAIT, highlighting the roles of HPA-specific antibodies, particularly HPA-1a, in causing severe thrombocytopenia and intracranial hemorrhage in affected neonates. Current management strategies, including intravenous immunoglobulin and investigational therapies like Nipocalimab, are evaluated for their efficacy and limitations. The review also discusses promising antigen-specific therapies, such as effector-silent monoclonal antibodies and innovative approaches targeting alloantibody-producing B cells. Additionally, the potential of Chimeric Autoantibody Receptor (CAAR) T cell therapy for selective elimination of pathogenic B cells is examined. The necessity for a prophylactic strategy similar to RhD immunoprophylaxis in preventing FNAIT is emphasized, along with the importance of identifying at-risk pregnancies. The development of renewable monoclonal antibodies and suitable animal models are critical steps toward effective prevention and treatment of this disorder.