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Transfusion. 2009 Oct;49(10):2076-83. doi: 10.1111/j.1537-2995.2009.02240.x. Epub 2009 Jun 4.

The new platelet alloantigen Cab a: a single point mutation Gln 716 His on the alpha 2 integrin.

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Platelet Immunology Unit, INTS, Paris, France.



Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal alloimmunization against fetal platelet (PLT) antigens, inherited from the father and absent from maternal PLTs.


A 29-year-old mother gave birth to a severely thrombocytopenic newborn (16 x 10(9) PLTs/L) leading to PLT transfusion therapy associated with intravenous immunoglobulins. The outcome was uneventful. Maternal serum showed a specific positive reaction with the antigen-capture assay (monoclonal antibody [MoAb]-specific immobilization of PLT antigens) only when it was tested with the paternal PLTs and a panel of MoAbs against glycoprotein (GP)Ia-IIa (alpha(2)beta(1) integrin) suggesting the implication of a new PLT antigen.


Nucleotide sequence analysis of GPIa cDNA of the father and newborn showed a nucleotide substitution at position 2235 (2235G > T according to the international nomenclature). This substitution induces a Q716H amino acid change in the GPIa mature protein, located outside the I domain involved in cell adhesion for collagen. In vitro analysis of recombinant Chinese hamster ovary (CHO) cells expressing wild-type or mutant (Q716H) human GPIa allowed us to demonstrate that this single amino acid substitution is responsible and sufficient for inducing Cab(a) antigen expression. Adhesion of CHO cells to collagen was not modified by the Cab polymorphism, nor by the maternal anti-Cab(a) alloantibodies, indicating that the mutation does not affect the function of integrin alpha(2)beta(1). In a Caucasian population study, none of the 104 unrelated blood donors was found to be Cab(a)(+).


We describe here a new PLT alloantigen Cab(a) involved in a severe case of FNAIT. Laboratory investigation for the "common" PLT alloantigens is no longer sufficient to evaluate neonatal alloimmune thrombocytopenia in suspected cases.

[Indexed for MEDLINE]

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