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• W2072844657 endingPage "4456" @default.
• W2072844657 startingPage "4449" @default.
• W2072844657 abstract "We report here the identification and characterization of a new platelet alloantigen, Duva+, implicated in a case of neonatal thrombocytopenia. Immunochemical studies demonstrated that the epitope was localized on glycoprotein (GP) IIIa. Sequencing of the exons 2 to 15 of GP IIIa gene polymerase chain reaction products from both parents revealed a single base substitution 517C&gt;T (complementary DNA) present in a heterozygous state in DNA from the father leading to amino acid substitution Thr140Ile (ACC&gt;ATC) within the Arg-Gly-Asp binding domain of GP IIIa. Flow cytometry and immunoprecipitation studies of IIb-C517 or T517 IIIa transfected Cos cells allowed us to demonstrate this mutation was responsible for expression of the Duva+epitope. By polymerase chain reaction–single-strand conformational-polymorphism analysis, the mutated allele could not be detected in a population of 100 healthy unrelated donors, indicating a low frequency of occurrence. The Thr140/Ile dimorphism, localized 3 amino acids upstream from the Arg143 involved in the expression of HPA-4a, did not interfere with the binding of an anti–HPA-4a antibody in flow cytometry. Results of functional analysis of wild-type or mutated transfected CHO cells—(1) aggregation in the presence of Ca++ and soluble fibrinogen after complex activation by dithiothreitol, (2) adhesion on coated fibrinogen, (3) binding of monoclonal antibody PAC-1 or LIBS antibody D3, and (4) outside-in signaling—all suggest that the Thr140Ile polymorphism localized in the Arg-Gly-Asp binding domain of GP IIIa does not affect significantly, if at all, the integrin function. We have shown that the anti-Duva+ antibody may inhibit platelet GP IIb-IIIa function." @default.
• W2072844657 created "2016-06-24" @default.
• W2072844657 creator A5002900300 @default.
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• W2072844657 date "2002-06-15" @default.
• W2072844657 modified "2023-10-16" @default.
• W2072844657 title "A new platelet polymorphism Duva+, localized within the RGD binding domain of glycoprotein IIIa, is associated with neonatal thrombocytopenia" @default.
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• W2072844657 doi "https://doi.org/10.1182/blood.v99.12.4449" @default.
• W2072844657 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12036875" @default.
• W2072844657 hasPublicationYear "2002" @default.
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