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HPA-10w(b) (La(a)): genetic determination of a new platelet-specific alloantigen on glycoprotein IIIa and its expression in COS-7 cells

O Peyruchaud, F Bourre, MC Morel-Kopp, D Reviron, P Mercier, A Nurden and C Kaplan

Unite Mixte de Recherche (UMR) 5533 Centre National de la Recherche Scientifique (CNRS), Hopital Cardiologique, Pessac, France.

The heterodimeric complex glycoprotein (GP)IIb-IIIa, the fibrinogen receptor of platelets, carries numerous alloantigen systems. These polymorphisms 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 platelet destruction in the fetus. In this report, we describe the molecular characterization of a new alloantigen (La(a)) on GPIIIa responsible for neonatal alloimmune thrombocytopenia (NAIT). Using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) and DNA sequencing, we found a point mutation (G to A) in a heterozygous state on the GPIIIa gene leading to amino acid substitution Arg to Gln at position 62 of the mature protein. Transient expression of GPIIb-IIIa complexes in Cos-7 cells using wild-type or mutated GPIIIa cDNA allowed us to demonstrate that this mutation was responsible for expression of the La(a) epitope.

Volume 89, Issue 7, pp. 2422-2428, 04/01/1997
Copyright © 1997 by The American Society of Hematology


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