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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 Santoso, S. Articles by Kiefel, V. Search for Related Content PubMed PubMed Citation Articles by Santoso, S. Articles by Kiefel, V. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 94 No. 12 (December 15), 1999: pp. 4103-4111 A Point Mutation Thr799Met on the 2 Integrin Leads to the Formation of New Human Platelet Alloantigen Sita and Affects Collagen-Induced Aggregation Sentot Santoso, Julia Amrhein, Heiko A. Hofmann, Ulrich J.H. Sachs, Matthias M. Walka, Hartmut Kroll, and Volker Kiefel From the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University Giessen, Giessen, Germany; the Department of Neonatology, Virchow Hospital, Humboldt-University, Berlin, Germany; and the Institute for Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany. A new platelet-specific alloantigen, termed Sita, was identified in a severe case of neonatal alloimmune thrombocytopenia. The Sita alloantigen is of low frequency (1/400) in the German population. Immunochemical studies demonstrated that the Sita epitopes reside on platelet glycoprotein (GP) Ia. Nucleotide sequence analysis of GPIa cDNA derived from Sita-positive platelets showed C2531T2531 point mutation, resulting in Thr799Met dimorphism. Analysis of genomic DNA from 22 Sita-negative normal individuals showed that the Thr799 is encoded by ACG2532 (90.9%) or ACA2532 (9.1%). To establish a DNA typing technique, we elucidated the organization of the GPIa gene adjacent to the polymorphic bases. The introns (421 bp and 1.2 kb) encompass a 142-bp exon with the 2 polymorphic bases 2531 and 2532. Polymerase chain reaction-restriction fragment length polymorphism analysis on DNA derived from 100 donors using the restriction enzyme Mae III showed that the Met799 form of GPIa is restricted to Sita (+) phenotype. Analysis of stable Chinese hamster ovary transfectants expressing allele-specific recombinant forms of GPIa showed that anti-Sita exclusively reacted with the Glu505Met799, but not with the Glu505Thr799 and the Lys505Thr799 isoforms. In contrast, anti-Bra (HPA-5b) only recognized the Lys505Thr799 form, whereas anti-Brb (HPA-5a) reacted with both Glu505Thr799 and Glu505Met799 isoforms. These results demonstrated that the Met799 is responsible for formation of the Sita alloantigenic determinants, whereas amino acid 505 (Lys or Glu) specifically controls the expression of Bra and Brb epitopes, respectively. Platelet aggregation responses of Sita (+) individuals were diminished in response to collagen, indicating that the Thr799Met mutation affects the function of the GPIa/IIa complex. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. V. Vijayan and P. F. Bray Molecular Mechanisms of Prothrombotic Risk Due to Genetic Variations in Platelet Genes: Enhanced Outside-In Signaling Through the Pro33 Variant of Integrin {beta}3. Experimental Biology and Medicine, May 1, 2006; 231(5): 505 - 513. [Abstract] [Full Text] [PDF] T. Chavakis, T. Keiper, R. Matz-Westphal, K. Hersemeyer, U. J. Sachs, P. P. Nawroth, K. T. Preissner, and S. Santoso The Junctional Adhesion Molecule-C Promotes Neutrophil Transendothelial Migration in Vitro and in Vivo J. Biol. Chem., December 31, 2004; 279(53): 55602 - 55608. [Abstract] [Full Text] [PDF] U. J. H. Sachs, T. Chavakis, L. Fung, A. Lohrenz, J. Bux, A. Reil, A. Ruf, and S. Santoso Human alloantibody anti-Mart interferes with Mac-1-dependent leukocyte adhesion Blood, August 1, 2004; 104(3): 727 - 734. [Abstract] [Full Text] [PDF] T. Chavakis, S. Santoso, K. J. Clemetson, U. J. H. Sachs, I. Isordia-Salas, R. A. Pixley, P. P. Nawroth, R. W. Colman, and K. T. Preissner High Molecular Weight Kininogen Regulates Platelet-Leukocyte Interactions by Bridging Mac-1 and Glycoprotein Ib J. Biol. Chem., November 14, 2003; 278(46): 45375 - 45381. [Abstract] [Full Text] [PDF] S. Santoso, U. J.H. Sachs, H. Kroll, M. Linder, A. Ruf, K. T. Preissner, and T. Chavakis The Junctional Adhesion Molecule 3 (JAM-3) on Human Platelets is a Counterreceptor for the Leukocyte Integrin Mac-1 J. Exp. Med., September 2, 2002; 196(5): 679 - 691. [Abstract] [Full Text] [PDF] S. Santoso, V. Kiefel, I. G. Richter, U. J. H. Sachs, A. Rahman, B. Carl, and H. Kroll A functional platelet fibrinogen receptor with a deletion in the cysteine-rich repeat region of the beta 3 integrin: the Oea alloantigen in neonatal alloimmune thrombocytopenia Blood, February 15, 2002; 99(4): 1205 - 1214. [Abstract] [Full Text] [PDF]

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