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Max(a), a new low-frequency platelet-specific antigen localized on
glycoprotein IIb, is associated with neonatal alloimmune thrombocytopenia
P Noris, S Simsek, LG de Bruijne-Admiraal, L Porcelijn, E Huiskes, GJ van der Vlist, EF van Leeuwen, CE van der Schoot and AE von dem Borne
University of Pavia, IRCCS, Polyclinic S. Matteo, Italy.
We have identified a new platelet-specific alloantigen, Max(a), responsible
for a typical case of neonatal alloimmune thrombocytopenic purpura. The
maternal serum reacted strongly with paternal platelets in the platelet
immunofluorescence test, whereas platelet alloantigen typing showed that no
known human platelet antigen (HPA)-system was involved. In the monoclonal
antibody (MoAb)-specific immobilization of platelet antigens (MAIPA) assay,
the new antigen was located on the platelet membrane glycoprotein (GP)
IIb-IIIa complex, but immunoprecipitation and immunoblot experiments to
further localize the antigen failed. However, in the MAIPA assay, the
binding of the anti- Max(a) antibodies from the maternal serum was blocked
by two anti-GPIIb MoAbs. Thus, the antigen appeared to be located on GPIIb.
Analysis of the family lead to the identification of six additional Max(a+)
individuals. Three of these six individuals and the father were tested in
the platelet aggregation test and were found to be normal. In the analysis
of normal donors, three of 500 were typed positive for the new
platelet-specific antigen, indicating a phenotype frequency of 0.6% in the
normal population. Platelet RNA was isolated from the newborn's Max(a)+
father and from a healthy donor phenotyped as Max(a-), reverse-
transcribed, and the entire GPIIb coding region was amplified by polymerase
chain reaction. Subsequent nucleotide sequence analysis showed a single
G-->A substitution at position 2,603, predicting a
valine-->methionine amino acid substitution at position 837 of the
mature glycoprotein. This mutation abolished a BsiYI restriction site at
the cDNA level and a BstNI restriction site at genomic DNA level,
respectively. The genetic association between the new antigen and this
point mutation was confirmed by allele-specific restriction analysis on
cDNA and on genomic DNA, as well as by allele-specific primer amplification
on genomic DNA. The new mutation is 19 bp upstream of the mutation
underlying the HPA-3 system. Therefore, we also evaluated the association
between Mas and the HPA-3 polymorphism. So far, all Max(a+) individuals
were also found to be HPA-3b, whereas 50 HPA-3a individuals were all
Max(a-). This may indicate that Max(a) is a variant of the HPA- 3 allele.
Volume 86,
Issue 3,
pp. 1019-1026,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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