Human platelet antigen 1a-specific B-cell receptor (HPA-1a-specific BCR)

The Human platelet antigen 1a (HPA-1a)-specific B-cell receptor is a membrane-bound immunoglobulin on B lymphocytes that specifically recognizes the HPA-1a epitope on platelet integrin beta-3 (ITGB3) (Stuge et al., 2005, PMID: 16099877). This receptor is central to the pathogenesis of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT), a condition where an HPA-1a-negative mother develops an immune response against HPA-1a-positive fetal platelets (Kjeldsen-Kragh et al., 2020, PMID: 32653245). Upon antigen recognition, these B cells proliferate and differentiate into plasma cells that secrete anti-HPA-1a IgG antibodies, which cross the placenta and mediate fetal platelet destruction (Eksteen et al., 2017, PMID: 28416603). Therapeutic targeting of the HPA-1a-specific BCR aims to selectively deplete or inhibit the pathogenic B-cell population, thereby preventing the production of harmful antibodies without inducing broad immunosuppression (Ghevaert et al., 2008, PMID: 18268174). Experimental approaches include the use of recombinant HPA-1a antigens or chimeric molecules designed to bind the BCR and trigger apoptosis or clearance of the specific B-cell clones. This precision medicine strategy is currently being explored as a safer and more effective alternative to current standard-of-care treatments like intravenous immunoglobulin (IVIG).

Other names

Anti-HPA-1a B-cell receptorHPA-1a BCRIntegrin beta-3 (HPA-1a variant) specific B-cell receptorHuman platelet antigen 1a-specific BCR

Selective binding to HPA-1a-specific B-cell receptors to induce cell death, internalization, or inhibition of B-cell differentiation into antibody-secreting plasma cells.