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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jallu, V. Articles by Kaplan, C. Search for Related Content PubMed PubMed Citation Articles by Jallu, V. Articles by Kaplan, C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Transfusion Medicine Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2002, Vol. 99, No. 12, pp. 4449-4456 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A new platelet polymorphism Duva+, localized within the RGD binding domain of glycoprotein IIIa, is associated with neonatal thrombocytopenia Vincent Jallu, Marc Meunier, Maryline Brément, and Cécile Kaplan From the Platelet Unit, INTS, Paris, France; and Pediatric Unit, CH, Fécamp, France. 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>T (complementary DNA) present in a heterozygous state in DNA from the father leading to amino acid substitution Thr140Ile (ACC>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 signalingall 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. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Kaplan-Gouet, L. Porcelijn, P. Vanlieferinghen, E. Julien, F. Bianchi, C. Martageix, and V. Jallu Anti-HPA-9bw (Maxa+) Feto-Maternal Alloimmunization and Clinically Severe Neonatal Thrombocytopenia: Difficulties in Diagnosis and Therapy, Report on 12 Cases. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 2066 - 2066. [Abstract]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020