Alloimmunization To The Platelet Antigen Human Platelet Antigen-1a And Characterization Of The Helper T-Cell Responses In Fetomaternal Alloimmune Thrombocytopenia

The major cause of severe FMAIT in Caucasians is fetal-maternal incompatibility for the human platelet antigen HPA-1a, which leads to the production of maternal anti-HPA-1a alloantibodies that cross the placenta and cause thrombocytopenia. The estimated incidence of severe FMAIT is approximately 1 in 1100 neonates, and the clinical manifestations range from mild purpura to intracranial hemorrhage and death. At present, there are no preventative measures or antenatal routine screening procedures in place to identify women at risk of HPA-1a allointmunization, nor reliable predictors of severe fetal disease, although maternal responsiveness is associated with DR52a (DRB3*0101). nAnti-HPA-1a production depends on antigen specific T helper lymphocytes that recognize HPA-a peptides bound to MHC molecules on antigen-presenting cells (APC). The core epitope on HPA-1a responsible for the alloimmune response has been identified by a combination of functional studies with immune lymphocytes and helper T cell clones, peptide binding and antigen processing studies. This dominant epitope has the potential to prevent or reverse the anti-HPA-1a response in women if used to induce tolerance.