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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1205-1214
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
A functional platelet fibrinogen receptor with a deletion in the
cysteine-rich repeat region of the  3 integrin: the
Oea alloantigen in neonatal alloimmune
thrombocytopenia
Sentot Santoso,
Volker Kiefel,
Ina G. Richter,
Ulrich J. H. Sachs,
Abdul Rahman,
Bettina Carl, and
Harmut Kroll
From the Institute for Clinical Immunology and
Transfusion Medicine, Justus Liebig University Giessen, Germany; and
Department of Transfusion Medicine, University of Rostock, Germany.
This report describes a new low-frequency alloantigen,
Oea, responsible for a case of neonatal alloimmune
thrombocytopenia (NAIT). In a population study none of 600 unrelated
blood donors was an Oea carrier. By immunochemical studies
the Oea antigen could be assigned to platelet glycoprotein
(GP) IIIa. Sequencing of GPIIIa complementary DNA from an
Oea (+) individual showed deletion of a lysine residue at
position 611 ( Lys611). Analysis of 20 Oea
( ) and 3 Oea (+) individuals showed that the
Lys611 form of GPIIIa was related to the phenotype.
Anti-Oea reacted with the Lys611, but not
with the wild-type isoforms on stable transfectants expressing GPIIIa,
indicating that Lys611 directly induces the expression
of Oea epitopes. Under nonreducing conditions the
Pro33Lys611 variant migrated with a slightly
decreased molecular weight compared to the
Pro33Lys611 isoform suggesting that
Lys611 has an influence on the disulfide bonds of
GPIIIa. The Pro33Lys611 GPIIIa could undergo
conformational changes and bind to fibrinogen in a similar manner as
the Pro33Lys611 isoform. No
difference was found in the tyrosine phosphorylation of
pp125FAK, suggesting that Lys611 has no
effect on integrin function. In contrast to all other low-frequency
antigens, the Lys611 isoform was associated with the
HPA-1b, but not with the high frequency HPA-1a allele. Comparison with
GPIIIa DNA from nonhuman primates indicated that the HPA-1a allele
represents the ancestral form of GPIIIa. It can be assumed that the
Oea form did arise as a result of a mutational event from
an already mutated GPIIIa allele.
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U. J. H. Sachs, C. L. Andrei-Selmer, A. Maniar, T. Weiss, C. Paddock, V. V. Orlova, E. Y. Choi, P. J. Newman, K. T. Preissner, T. Chavakis, et al.
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J. Biol. Chem.,
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282(32):
23603 - 23612.
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