Sra, a private platelet antigen on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia

A new platelet alloantigen, Sra, is described that was defined by an alloantibody detected in the serum of a healthy mother who delivered a child with typical clinical signs of neonatal alloimmune thrombocytopenia (NAIT). The antibody reacted strongly with the child's and father's platelets, but not with platelets of the mother or with those of a highly selected panel representing all known platelet alloantigens. Platelets from 300 unselected normal blood donors also tested negative, suggesting a phenotype frequency in the German population of less than 0.01. The antigen was present in 9 of 20 members within three generations of the paternal family, indicating autosomal codominant inheritance. By immunochemical analysis using a glycoprotein (GP)-specific immunoassay and a variety of GP IIb/IIIa- specific monoclonal antibodies for antigen immobilization (MAIPA assay), radioimmunoassay, and Western blotting, we could show that the antigen resides on a 68-Kd proteolytic fragment of GP IIIa. Immunogenetic data and gene dosage studies revealed that the Sra antigen is not related to any of the other known platelet alloantigens. In accordance with established criteria, the Sra antigen represents the first example of a “private” platelet alloantigen that bears significance in rare instances of NAIT.