HPA-10W(B) (LA-A) - GENETIC DETERMINATION OF A NEW PLATELET-SPECIFIC ALLOANTIGEN ON GLYCOPROTEIN IIIA AND ITS EXPRESSION IN COS-7 CELLS

The heterodimeric complex glycoprotein (GP)IIb-IIIa, the fibrinogen re ceptor of platelets, carries numerous alloantigen systems. These polym orphisms are responsible for the immune response after transfusion or during pregnancy, In the latter case, the mother develops an antibody against an epitope present on fetal platelets, and this results in pla telet destruction in the fetus. In this report, we describe the molecu lar characterization of a new alloantigen (La-a) on GPIIIa responsible for neonatal alloimmune thrombocytopenia (NAIT). Using polymerase cha in reaction (PCR)-single-strand conformation polymorphism (SSCP) and D NA sequencing, we found a point mutation (G to A) in a heterozygous st ate on the GPIIIa gene leading to amino acid substitution Arg to Gin a t position 62 of the mature protein, Transient expression of GPIIb-III a complexes in Cos-7 cells using wild-type or mutated GPIIIa cDNA allo wed us to demonstrate that this mutation was responsible for expressio n of the La-a epitope. (C) 1997 by The American Society of Hematology.