Integrin beta-3 (ITGB3) (ITGB3)

Integrin beta-3 (ITGB3), also known as platelet glycoprotein GPIIIa, is a critical transmembrane protein that forms a heterodimeric complex with Integrin alpha-IIb (GPIIb) to create the αIIbβ3 receptor, the primary mediator of platelet aggregation and hemostasis [1, 2]. The Human Platelet Antigen 1a (HPA-1a) epitope is a specific polymorphic site on GPIIIa defined by a Leucine residue at position 33 of the mature protein, which is the most frequent target of maternal alloantibodies in Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) [2, 4]. In FNAIT, maternal IgG antibodies against the fetal HPA-1a epitope cross the placenta, leading to the destruction of fetal platelets and a significant risk of intracranial hemorrhage [4]. Therapeutic strategies specifically targeting the HPA-1a epitope, such as the monoclonal antibody RLYB212, aim to prevent maternal sensitization by rapidly clearing HPA-1a-positive fetal platelets from the maternal circulation [3]. Beyond its role in alloimmune disorders, the broader GPIIb/IIIa complex is a major pharmacological target for antiplatelet drugs like abciximab and eptifibatide, which are used to prevent thrombotic complications in acute coronary syndromes by blocking fibrinogen binding [5]. Sources: [1] UniProt P05106; [2] PMID: 30633415; [3] Rallybio Pipeline Data; [4] PMID: 31550302; [5] StatPearls: Glycoprotein IIb/IIIa Inhibitors.

Other names

Platelet glycoprotein GPIIIaGPIIIaCD61Human Platelet Antigen 1aHPA-1aIntegrin subunit beta 3Platelet membrane glycoprotein IIIa

Prevention of maternal alloimmunization through antibody-mediated clearance of HPA-1a positive fetal platelets or epitope masking; competitive inhibition of fibrinogen binding to the αIIbβ3 complex to prevent platelet aggregation.